Nothing Special   »   [go: up one dir, main page]

EP1797877A1 - Joint use of sulfonamide based compound with angiogenesis inhibitor - Google Patents

Joint use of sulfonamide based compound with angiogenesis inhibitor Download PDF

Info

Publication number
EP1797877A1
EP1797877A1 EP05785820A EP05785820A EP1797877A1 EP 1797877 A1 EP1797877 A1 EP 1797877A1 EP 05785820 A EP05785820 A EP 05785820A EP 05785820 A EP05785820 A EP 05785820A EP 1797877 A1 EP1797877 A1 EP 1797877A1
Authority
EP
European Patent Office
Prior art keywords
group
optionally substituted
hydrogen atom
methyl
methoxy
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP05785820A
Other languages
German (de)
French (fr)
Other versions
EP1797877A4 (en
Inventor
Takashi Tsukuba Research Labs. Eisai Co. Ltd OWA
Yoichi Tsukuba Research Labs. Eisai Co. Ltd OZAWA
Taro Tsukuba Research Labs. Eisai Co. Ltd. SEMBA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eisai R&D Management Co Ltd
Original Assignee
Eisai Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Eisai Co Ltd filed Critical Eisai Co Ltd
Priority to EP11169343A priority Critical patent/EP2364699A1/en
Publication of EP1797877A1 publication Critical patent/EP1797877A1/en
Publication of EP1797877A4 publication Critical patent/EP1797877A4/en
Withdrawn legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39541—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against normal tissues, cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the present invention relates to novel pharmaceutical, compositions and kits, which are characterized by comprising a sulfonamide-including compound in combination with an angiogenesis inhibitor, more specifically with a VEGF inhibitor or a FGF inhibitor.
  • Cancer chemotherapeutics conventionally used include alkylating agents such as cyclophosphamide, antimetabolites such as methotrexate and fluorouracil, antibiotics such as adriamycin, mitomycin and bleomycin, plant-derived agents such as taxol, vincristine and etoposide, as well as metal complexes such as cisplatin.
  • alkylating agents such as cyclophosphamide
  • antimetabolites such as methotrexate and fluorouracil
  • antibiotics such as adriamycin, mitomycin and bleomycin
  • plant-derived agents such as taxol, vincristine and etoposide
  • metal complexes such as cisplatin.
  • sulfonamide-including compounds have been reported as useful anti-tumor agents (1-4) .
  • E7070 N-(3-chloro-1H-indol-7-yl)-4-sulfamoylbenzenesulfonamide
  • E7820 N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide
  • LY186641 N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide
  • LY295501 N-(2,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide
  • LY295501 N-(2,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide
  • E7820 which is one of the sulfonamide-including compounds and an angiogenesis inhibitor produces excellent angiogenesis inhibitory activity and anti-tumor activity (5) .
  • the present invention was made under such circumstances, and the problem to be solved by the invention is to find out pharmaceutical compositions and kits having excellent angiogenesis inhibitory activity and/or anti-tumor activity.
  • the inventors of the present invention have found that there is a high correlation between the pattern of gene expression changes and cell growth inhibitory activity provided by E7820, E7070, LY186641, LY295501, LY573636 or CQS or combinations thereof in experiments using DNA microarrays and cancer cell line panels. Likewise, in cell growth inhibition assays, the inventors have also found that cancer cell lines resistant to E7070 have cross-resistance to E7820, LY186641, LY295501, LY ASAP, LY573636 and CQS.
  • E7820 has been reported to show excellent angiogenesis inhibitory activity and anti-tumor activity when used in combination with an angiogenesis inhibitor ( WO03/074045 ).
  • E7070, LY186641, LY295501, LY-ASAP, LY573636 or CQS or combinations thereof are also believed to show excellent angiogenesis inhibitory activity and anti-tumor activity when used in combination with an angiogenesis inhibitor;
  • sulfonamide-including compounds preferably E7070, LY186641, LY295501, LY-ASAP, LY573636 or CQS or combinations thereof, have now been found to provide useful pharmaceutical compositions and kits when combined with angiogenesis inhibitors.
  • the present invention is directed to the following.
  • the above sulfonamide-including compound includes at least one compound selected from the group consisting of
  • the above sulfonamide-including compound may be a compound of Formula (IX): or a pharmacologically acceptable salt thereof or a solvate thereof
  • the present invention is also directed to the following.
  • the above sulfonamide-including compound includes a compound of Formula (XIV): [wherein
  • the above VEGF receptor kinase inhibitor may include at least one compound selected from the group consisting of:
  • the above VEGF receptor kinase inhibitor may be 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  • the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity.
  • the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity and enables them to be used for cancer treatment or angiogenesis inhibition.
  • sulfonamide-including compounds preferably E7820, with VEGF receptor kinase inhibitors
  • the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity and enables them to be used for cancer treatment or angiogenesis inhibition.
  • halogen atom refers to a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
  • C 1-6 alkyl group refers to a linear or branched alkyl group containing 1 to 6 carbon atoms. Specific examples include a methyl group, an ethyl group, a 1-propyl group (i.e., a n-propyl group), a 2-propyl group (i.e., an i(iso)-propyl group or an isopropyl group), a 2-methyl-1-propyl group (i.e., an i-butyl group or an isobutyl group), a 2-methyl-2-propyl group (i.e., a t(tert)-butyl group), a 1-butyl group (i.e., a n-butyl group), a 2-butyl group (i.e., a s(sec)-butyl group), a 1-pentyl group (i.e., a n-pentyl group or an amyl
  • C 1-6 alkyl group may include a methyl group, an ethyl group, a 1-propyl group, a 2-propyl group, a 2-methyl-1-propyl group, a 2-methyl-2-propyl group, a 1-butyl group, and a 2-butyl group.
  • C 1-6 alkylene group refers to a divalent group derived by removing any one hydrogen atom from the "C 1-6 alkyl group” defined above. Specific examples include a methylene group, a 1,2-ethylene group, a 1,1-ethylene group, a 1,3-propylene group, a tetramethylene group, a pentamethylene group, and a hexamethylene group.
  • C 2-6 alkenyl group refers to a linear or branched alkenyl group having one double bond and containing 2 to 6 carbon atoms. Specific examples include an ethenyl group (i.e., a vinyl group), a 1-propenyl group, a 2-propenyl group (i.e., an allyl group), a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a pentenyl group, and a hexenyl group.
  • C 2-6 alkynyl group refers to a linear or branched alkynyl group having one triple bond and containing 2 to 6 carbon atoms. Specific examples include an ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, a pentynyl group, and a hexynyl group.
  • C 3-8 cycloalkyl group refers to a monocyclic or bicyclic saturated aliphatic hydrocarbon group containing 3 to 8 carbon atoms. Specific examples include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a bicyclo[2.1.0]pentyl group, a bicyclo[3.1.0]hexyl group, a bicyclo[2.1.1]hexyl group, a bicyclo[4.1.0]heptyl group, a bicyclo[2.2.1]heptyl group (i.e., a norbornyl group), a bicyclo[3.3.0]octyl group, a bicyclo[3.2.1]octyl group, and a bicyclo[2.2.2]octyl group.
  • C 3-8 cycloalkyl group may include a cyclopropyl group, a cyclobutyl group, and a cyclopentyl group.
  • C 6-10 aryl group refers to an aromatic cyclic hydrocarbon group containing 6 to 10 carbon atoms. Specific examples include a phenyl group, a 1-naphthyl group, a 2-naphthyl group, an indenyl group, and an azulenyl group.
  • C 6-10 aryl group may include a phenyl group.
  • heteroatom refers to a nitrogen atom, an oxygen atom or a sulfur atom.
  • the term "5- to 10-membered heteroaryl group” refers to an aromatic cyclic group having 5 to 10 ring member atoms, 1 to 5 of which are heteroatoms.
  • Specific examples include a furyl group, a thienyl group, a pyrrolyl group, an imidazolyl group, a triazolyl group, a tetrazolyl group, a thiazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, an isothiazolyl group, a furazanyl group, a thiadiazolyl group, an oxadiazolyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl group, a pyrimidinyl group, a triazinyl group, a purinyl group, a pteridinyl group, a quinolyl group,
  • Preferred examples of the "5- to 10-membered heteroaryl group” may include a furyl group, a thienyl group, a pyrrolyl group, an imidazolyl group, a thiazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, an isothiazolyl group, a pyridyl group, and a pyrimidinyl group.
  • 3- to 10-membered non-aromatic heterocyclic group refers to a non-aromatic cyclic group characterized by:
  • Preferred examples of the "3- to 10-membered non-aromatic heterocyclic group” may include an aziridinyl group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, an azepanyl group, a piperazinyl group, a diazepanyl group, a morpholinyl group, a thiomorpholinyl group, a 1,1-dioxothiomorpholinyl group, a tetrahydrofuryl group, and a tetrahydropyranyl group.
  • C 1-6 alkoxy group refers to a group having an oxygen atom attached to the end of the "C 1-6 alkyl group” defined above.
  • Specific examples include a methoxy group, an ethoxy group, a 1-propoxy group (i.e., a n-propoxy group), a 2-propoxy group (i.e., an i-propoxy group), a 2-methyl-1-propoxy group (i.e., an i-butoxy group), a 2-methyl-2-propoxy group (i.e., a t-butoxy group), a 1-butoxy group (i.e., a n-butoxy group), a 2-butoxy group (i.e., a s-butoxy group), a 1-pentyloxy group, a 2-pentyloxy group, a 3-pentyloxy group, a 2-methyl-1-butoxy group, a 3-methyl-1-butoxy group, a 2-methyl-2-butoxy group, a 3-
  • C 1-6 alkoxy group may include "C 1-4 alkoxy groups,” as exemplified by a methoxy group, an ethoxy group, a 1-propoxy group, a 2-propoxy group, a 2-methyl-1-propoxy group, a 2-methyl-2-propoxy group, a 1-butoxy group, and a 2-butoxy group.
  • C 1-6 alkylthio group refers to a group having a sulfur atom attached to the end of the "C 1-6 alkyl group” defined above. Specific examples include a methylthio group, an ethylthio group, a 1-propylthio group (i.e., a n-propylthio group), a 2-propylthio group (i.e., an i-propylthio group or an isopropylthio group), a 2-methyl-1-propylthio group (i.e., an i-butylthio group or an isobutylthio group), a 2-methyl-2-propylthio group (i.e., a t(tert)-butylthio group), a 1-butylthio group (i.e., a n-butylthio group), a 2-butylthio group (i.e., a s(sec)-
  • C 1-6 alkylthio group may include "C 1-4 alkylthio groups,” as exemplified by a methylthio group, an ethylthio group, a 1-propylthio group, a 2-propylthio group, a 2-methyl-1-propylthio group, a 2-methyl-2-propylthio group, a 1-butylthio group, and a 2-butylthio group.
  • C 3-8 cycloalkoxy group refers to a group having an oxygen atom attached to the end of the "C 3-8 cycloalkyl group” defined above.
  • Specific examples include a cyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a cyclohexyloxy group, a cycloheptyloxy group, a cyclooctyloxy group, a bicyclo[2.1.0]pentyloxy group, a bicyclo[3.1.0]hexyloxy group, a bicyclo[2.1.1]hexyloxy group, a bicyclo[4.1.0]heptyloxy group, a bicyclo[2.2.1]heptyloxy group (i.e., a norbornyloxy group), a bicyclo[3.3.0]octyloxy group, a bicyclo[3.2.1]octyloxy group, and a bicyclo
  • C 3-8 cycloalkoxy group may include a cyclopropoxy group, a cyclobutoxy group, and a cyclopentyloxy group.
  • the term "mono-C 1-6 alkylamino group” refers to an amino group whose one hydrogen atom is replaced by the "C 1-6 alkyl group” defined above. Specific examples include a methylamino group, an ethyl amino group, a 1-propylamino group (i.e., a n-propylamino group), a 2-propylamino group (i.e., an i-propylamino group), a 2-methyl-1-propylamino group (i.e., an i-butylamino group), a 2-methyl-2-propylamino group (i.e., a t-butylamino group), a 1-butylamino group (i.e., a n-butylamino group), a 2-butylamino group (i.e., a s-butylamino group), a 1-pentylamino group, a 2-pentylamino group,
  • di-C 1-6 alkylamino group refers to an amino group whose two hydrogen atoms are replaced by the same or different "C 1-6 alkyl groups" defined above.
  • Specific examples include an N,N-dimethylamino group, an N,N-diethylamino group, an N,N-di-n-propylamino group, an N,N-di-i-propylamino group, an N,N-di-n-butylamino group, an N,N-di-i-butylamino group, an N,N-di-s-butylamino group, an N,N-di-t-butylamino group, an N-ethyl-N-methylamino group, an N-n-propyl-N-methylamino group, an N-i-propyl-N-methylamino group, an N-n-butyl-N-methylamino group, an N-i
  • C 2-7 acyl group refers to a carbonyl group, to which the "C 1-6 alkyl group” defined above is attached. Specific examples include, for example, an acetyl group, a propionyl group, an isopropionyl group, a butyryl group, an isobutyryl group, a valeryl group, an isovaleryl group, and a pivaloyl group.
  • C 2-7 alkoxycarbonyl group refers to a carbonyl group, to which the "C 1-6 alkoxy group” defined above is attached. Specific examples include, for example, a methoxycarbonyl group, an ethoxycarbonyl group, a 1-propyloxycarbonyl group, a 2-propyloxycarbonyl group, and a 2-methyl-2-propoxy group (i.e., a t-butoxycarbonyl group).
  • C 2-5 alkoxycarbonyl group refers to a carbonyl group, to which the "C 1-4 alkoxy group” defined above is attached. Specific examples include, for example, a methoxycarbonyl group, an ethoxycarbonyl group, a 1-propyloxycarbonyl group, a 2-propyloxycarbonyl group, and a 2-methyl-2-propoxy group.
  • substituents include, for example, a halogen atom, a hydroxyl group, a thiol group, a nitro group, a cyano group, a formyl group, a carboxyl group, an amino group, a silyl group, a C 1-6 alkyl group, a C 2-6 alkenyl group, a C 2-6 alkynyl group, a C 3-8 cycloalkyl group, a C 6-10 aryl group, a 5- to 10-membered heteroaryl group, a 3- to 10-membered non-aromatic heterocyclic group, a C 1-6 alkoxy group, a C 1-6 alkylthio group,
  • the sulfonamide-including compound includes compounds of the following Formula (I):
  • E represents -O-, -N(CH 3 )-, -CH 2 -, -CH 2 CH 2 - or -CH 2 O-
  • D represents -CH 2 - or -O-
  • R 1a represents a hydrogen atom or a halogen atom
  • R 2a represents a halogen atom or a trifluoromethyl group.
  • the compounds of Formula (I) according to the present invention can be prepared in a known manner, for example as described in European Patent Publication No. 0222475A1 .
  • a preferred compound is LY186641 or LY295501.
  • LY186641 refers to N-[[(4-chlorophenyl)amino]carbonyl]-2,3-dihydro-1H-indene-5-sulfonamide and its structural formula is shown in the following Formula (VII):
  • LY186641 can be prepared in a known manner, for example as described in European Patent Publication No. 0222475A1 .
  • LY295501 refers to N-[[(3,4-dichlorophenyl)amino]-carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide and its structural formula is shown in the following Formula (VIII):
  • LY295501 can be prepared in a known manner, for example as described in European Patent Publication No. 0222475A1 and/or European Patent Publication No. 0555036A2 .
  • the sulfonamide-including compound also includes compounds of the following Formula (II):
  • J represents -O- or -NH-
  • R 1b represents a hydrogen atom, a halogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 1-4 alkoxy group, an optionally substituted C 1-4 alkylthio group, an optionally substituted C 2-5 alkoxycarbonyl group, a nitro group, an azido group, -O(SO 2 )CH 3 , -N(CH 3 ) 2 , a hydroxyl group, a phenyl group, a substituted phenyl group, a pyridinyl group, a thienyl group, a furyl group, a quinolinyl group or a triazole group
  • R 2b represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-5 alkoxycarbonyl group, an optionally substituted C
  • the "C 1-6 alkyl group” may preferably include a methyl group, an ethyl group, a 1-propyl group, a 2-propyl group, a 2-methyl-1-propyl group, a 2-methyl-2-propyl group, a 1-butyl group, and a 2-butyl group. Among them, most preferred are a methyl group, an ethyl group, a 1-propyl group, and a 2-propyl group.
  • the optionally substituted C 1-6 alkyl group may be, for example, a trifluoromethyl group.
  • the "C 1-4 alkoxy group” may preferably include a methoxy group, an ethoxy group, a 1-propoxy group, a 2-propoxy group, and a 1-butoxy group.
  • the optionally substituted C 1-4 alkoxy group may be, for example, -OCF 3 .
  • the "C 1-4 alkylthio group” may preferably include a methylthio group, an ethylthio group, a 1-propylthio group, a 2-propylthio group, a 2-methyl-1-propylthio group, a 2-methyl-2-propyl group, a 1-butylthio group, and a 2-butylthio group.
  • the optionally substituted C 1-4 alkylthio group may be, for example, -SCF 3 .
  • the "C 2-5 alkoxycarbonyl group” may preferably include a methoxycarbonyl group, an ethoxycarbonyl group, a 1-propyloxycarbonyl group, a 2-propyloxycarbonyl group, and a t-butoxycarbonyl group.
  • examples of substituents to be introduced may include those exemplified by a C 1-6 alkyl group, a C 1-4 alkoxy group, an amino group, a hydroxyl group, a halogen atom or a silyl group.
  • the compounds of Formula (II) according to the present invention can be prepared in a known manner, for example as described in International Publication No. WO02/098848 .
  • a preferred compound is LY-ASAP.
  • LY-ASAP refers to N-(2,4-dichlorobenzoyl)-4-chlorophenylsulfonamide and its structural formula is shown in the following Formula (XI):
  • LY-ASAP can be prepared in a known manner, for example as described in International Publication No. WO02/098848 .
  • the sulfonamide-including compound may also include LY573636.
  • LY573636 refers to N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide and its structural formula is shown in the following Formula (III):
  • LY573636 is preferably in sodium salt form.
  • LY573636 can be prepared in a known manner, for example, in the same manner as described in International Publication No. WO02/098848 , starting with commercially available 5-bromothiophene-2-sulfonyl chloride and 2,4-dichlorobenzoic acid.
  • the sulfonamide-including compound may also include CQS.
  • CQS refers to 2-sulfanylamido-5-chloroquinoxaline and its structural formula is shown in the following Formula (IV):
  • CQS can be prepared in a known manner, for example as described in J. Am. Chem. Soc., 1947, 71, 6-10 .
  • the sulfonamide-including compound may also include E7070.
  • E7070 refers to N-(3-chloro-1H-indol-7-yl)4-sulfamoylbenzenesulfonamide and its structural formula is shown in the following Formula (IX):
  • E7070 can be prepared in a known manner, for example as described in International Publication No. WO95/07276 or in Example 19 of JP 7-165708 A .
  • the sulfonamide-including compound also includes compounds of the following Formula (XIV).
  • R 1 , R 2 and R 3 which may be the same or different, each independently represents a hydrogen atom or a lower alkyl group.
  • the "optionally substituted monocyclic or bicyclic aromatic ring" defined for the ring A refers to an aromatic hydrocarbon or an aromatic heterocyclic ring containing at least one of a nitrogen atom, an oxygen atom and a sulfur atom. Such a ring may have 1 to 3 substituents.
  • Examples of major aromatic rings encompassed by the ring A may include pyrrole, pyrazole, imidazole, thiophene, furan, thiazole, oxazole, benzene, pyridine, pyrimidine, pyrazine, pyridazine, naphthalene, quinoline, isoquinoline, phthalazine, naphthylizine, quinoxaline, quinazoline, cinnoline, indole, isoindole, indolizine, indazole, benzofuran, benzothiophene, benzoxazole, benzimidazole, benzopyrazole, and benzothiazole.
  • substituents may include an optionally lower alkyl- or lower cycloalkyl-substituted amino group, a lower alkyl group, a lower alkoxy group, a hydroxyl group, a nitro group, a mercapto group, a cyano group, a lower alkylthio group, a halogen atom, a group represented by the formula -a-b [wherein a represents a single bond, -(CH 2 ) k -, -O-(CH 2 ) k -, -S-(CH 2 ) k - or -N(R 3 )-(CH 2 ) k -, k represents an integer of 1 to 5, R 3 represents a hydrogen atom or a lower alkyl group, and b represents -CH 2 - d (wherein d represents an optionally lower alkyl-substituted amino group
  • these alkyl groups may together form a 5- or 6-membered ring.
  • these groups may form an oxo group or a thioxo group by taking the resonance structure.
  • the "optionally substituted 6-membered cyclic unsaturated hydrocarbon” or the “optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom" defined for the ring B refers to, for example, benzene or pyridine whose unsaturated bonds may be partially hydrogenated. Such a ring may have one or more substituents, which may be the same or different.
  • the "optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms" defined for the ring C refers to pyrrole, pyrazole or imidazole whose unsaturated bonds may be partially hydrogenated. Such a ring may have one or two substituents, which may be the same or different.
  • Z represents -N(R 2 )-.
  • R 2 may be the same as or different from R 1 described later and represents a hydrogen atom or a lower alkyl group.
  • substituents which may be on the rings B and C include a halogen atom, a cyano group, a lower alkyl group, a lower alkoxy group, a hydroxyl group, an oxo group, a group represented by the formula -C(O)-r (wherein r represents a hydrogen atom, an optionally lower alkyl-substituted amino group, a lower alkyl group, a lower alkoxy group or a hydroxyl group), an optionally lower alkyl-substituted amino group, and a trifluoromethyl group.
  • R 3 represents a hydrogen atom or a lower alkyl group.
  • R 1 may be the same as or different from R 2 and represents a hydrogen atom or a lower alkyl group.
  • lower cycloalkyl (group) found in the definition of substituents which may be on the ring A refers to a cycloalkyl group containing 3 to 8 carbon atoms and has the same meaning as the "C 3-8 cycloalkyl group” mentioned above.
  • Examples of such a lower cycloalkyl group include a cyclopropyl group, a cyclopentyl group, and a cyclohexyl group.
  • the “lower alkylthio (group)” refers to an alkylthio group derived from the above lower alkyl group and has the same meaning as the "C 1-6 alkylthio group” mentioned above.
  • lower alkoxy (group) found in the definition of substituents which may be on the rings A, B and C refers to, for example, a lower alkoxy group derived from the above lower alkyl group, as exemplified by a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, and a tert-butoxy group. Among them, most preferred are a methoxy group and an ethoxy group.
  • examples of the "halogen atom” include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • the compounds of Formula (XIV) according to the present invention can be prepared in a known manner, for example as described in International Publication No. WO95/07276 and/or JP 7-165708 A .
  • a preferred compound is the E7070 mentioned above or E7820.
  • E7820 refers to N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide and its structural formula is shown in the following Formula (X):
  • E7820 can be prepared in a known manner, for example as described in International Publication No. WO00/50395 .
  • sulfonamide-including compounds may form pharmacologically acceptable salts with acids or bases.
  • the compounds according to the present invention also encompass these pharmacologically acceptable salts.
  • salts with acids include inorganic acid salts (e.g., hydrochloride salt, hydrobromide salt, sulfate salt, phosphate salt), as well as salts with organic acids such as formic acid, acetic acid, lactic acid, succinic acid, fumaric acid, maleic acid, citric acid, tartaric acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and trifluoroacetic acid.
  • inorganic acid salts e.g., hydrochloride salt, hydrobromide salt, sulfate salt, phosphate salt
  • organic acids such as formic acid, acetic acid, lactic acid, succinic acid, fumaric acid, maleic acid, citric acid,
  • salts with bases include alkali metal salts (e.g., sodium salt, potassium salt), alkaline earth metal salts (e.g., calcium salt, magnesium salt), salts with organic bases such as trimethylamine, triethylamine, pyridine, picoline, dicyclohexylamine, N,N'-dibenzylethylenediamine, arginine and lysine (organic amine salts), as well as ammonium salts.
  • alkali metal salts e.g., sodium salt, potassium salt
  • alkaline earth metal salts e.g., calcium salt, magnesium salt
  • salts with organic bases such as trimethylamine, triethylamine, pyridine, picoline, dicyclohexylamine, N,N'-dibenzylethylenediamine, arginine and lysine (organic amine salts), as well as ammonium salts.
  • these sulfonamide-including compounds may be in anhydride form or may form solvates such as hydrates.
  • Solvates may be either hydrates or anhydrates, preferably hydrates.
  • Solvents available for use include water, alcohols (e.g., methanol, ethanol, n-propanol) and dimethylformamide..
  • the compounds according to the present invention also encompass their solvates and/or optical isomers.
  • the compounds according to the present invention further encompass sulfonamide-including compounds that are metabolized in vivo by oxidation, reduction, hydrolysis, conjugation, etc.
  • the compounds according to the present invention encompass compounds that produce sulfonamide-including compounds when metabolized in vivo by oxidation, reduction, hydrolysis, etc.
  • the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity.
  • angiogenesis inhibitor is also referred to as an angiogenesis inhibitory agent in the following explanation.
  • the angiogenesis inhibitor is not limited in any way as long as it has an inhibitory activity on angiogenesis.
  • angiogenesis inhibitor include VEGF (vascular endothelial growth factor) inhibitors (e.g., VEGF receptor kinase inhibitors, anti-VEGF antibodies ( Cancer Research., 55, 5296-5301, 1995 )), FGF (fibroblast growth factor) inhibitors (e.g., FGF receptor kinase inhibitors, anti-FGF antibodies ( Cancer Research., 51, 6180-4, 1991 )), PDGF (platelet-derived growth factor) inhibitors (e.g., PDGF receptor kinase inhibitors ( J.
  • integrin inhibitors e.g., ⁇ v ⁇ 3 integrin inhibitors, ⁇ v ⁇ 5 integrin inhibitors ( Clinical Cancer Research., 6, 3056-61, 2000 )
  • endogenous inhibitors e.g., IL-12, Trombospondin-1, Endostatin, Angiostatin ( International J. Cancer., 78, 361-5, 1998 )
  • COX-2 inhibitors Annuals of N.Y Acad. Science., 84-6, 1999
  • matrix metalloprotein inhibitors International J.
  • Pancreatol., 21, 1-12, 1997 as well as other inhibitors (e.g., farnesyltransferase inhibitors, nitric oxide inhibitors, angiotensin converting enzyme inhibitors, HMG-CoA reductase inhibitors, Vascular Target inhibitors, methionine aminopeptidase inhibitors ( Science., 282, 1324-1327, 1998 )).
  • Preferred examples are VEGF receptor kinase inhibitors, anti-VEGF antibodies, FGF receptor kinase inhibitors and anti-FGF antibodies, and more preferred examples are VEGF receptor kinase inhibitors and anti-VEGF antibodies.
  • the VEGF receptor kinase inhibitor may include, for example, compounds of Formula (XXIV):
  • the compounds of Formula (XXIV) can be prepared in a known manner, for example as described in International Publication No. WO02/032872 , International Publication No. WO2004/020434 , and/or International Publication No. WO2005/063713 .
  • the VEGF receptor kinase inhibitor may preferably include compounds of Formula (XXV): Formula (XXV) is a preferred example of the compounds of Formula (XXIV).
  • R 1e represents a group represented by the formula -V 1e -V 2e -V 3e (wherein V 1e represents an optionally substituted C 1-6 alkylene group; V 2e represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR 6e -, a group represented by the formula -SO 2 NR 6e -, a group represented by the formula -NR 6e SO 2 -, a group represented by the formula -NR 6e CO- or a group represented by the formula -NR 6e - (wherein R 6e represents a hydrogen atom, an optionally substituted C 1-6 alkyl group or an optionally substituted C 3-8 cycloalkyl group); and V 3e represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group
  • R 1e include a C 1-6 alkyl group.
  • R 1e may have one or more substituents selected from a 3- to 10-membered non-aromatic heterocyclic group which may have a C 1-6 alkyl group, a hydroxyl group, a C 1-6 alkoxy group, an amino group, a mono-C 1-6 alkylamino group and a di-C 1-6 alkylamino group.
  • R 1e include a methyl group or a group represented by any of the following formulae: (wherein R a3 represents a methyl group; R a1 represents a hydrogen atom or a hydroxyl group; and R a2 represents a methoxy group, an ethoxy group, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group).
  • R 1e include a methyl group or a 2-methoxyethyl group.
  • R 2e represents a cyano group, an optionally substituted C 1-6 alkoxy group, a carboxyl group, an optionally substituted C 2-7 alkoxycarbonyl group or a group represented by the formula -CONV e11 V e12 (wherein V e11 represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and V e12 represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalky
  • R 2e include a cyano group or a group represented by the formula -CONV e11 V e12 (wherein V e11 and V e12 are as defined above).
  • R 2e include a cyano group or a group represented by the formula -CONHV e16 (wherein V e16 represents a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, a C 1-6 alkoxy group or a C 3-8 cycloalkoxy group, provided that V e16 may have one or more substituents selected from a halogen atom, a cyano group, a hydroxyl group and a C 1-6 alkoxy group).
  • R 2e include a group represented by the formula - CONHV e17 (wherein V e17 represents a hydrogen atom, a C 1-6 alkyl group or a C 1-6 alkoxy group) .
  • R 2e include a group represented by the formula - CONHV e18 (wherein V e18 represents a hydrogen atom, a methyl group or a methoxy group).
  • Y 1 represents a group represented by the following formula: (wherein R 7e and R 8e each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C 1-6 alkyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 1-6 alkoxy group, a formyl group, an optionally substituted C 2-7 acyl group, an optionally substituted C 2-7 alkoxycarbonyl group or a group represented by the formula -CONV e1 V e2 (wherein V e1 and V e2 each independently represent a hydrogen atom or an optionally substituted C 1-6 alkyl group); and
  • W 1e and W 2e each independently represent an optionally substituted carbon atom or a nitrogen atom).
  • Preferred examples of Y 1 include a group represented by the following formula: (wherein R 71 represents a hydrogen atom or a halogen atom).
  • R 3e and R 4e each independently represent a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 2-7 acyl group or an optionally substituted C 2-7 alkoxycarbonyl group.
  • R 3e and R 4e include a hydrogen atom.
  • R 5e represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group.
  • R 5e include a hydrogen atom, a C 1-6 alkyl group, a C 3-8 cycloalkyl group or a C 6-10 aryl group (provided that R 5e may have one or more substituents selected from a halogen atom and a methanesulfonyl group).
  • R 5e include a methyl group, an ethyl group or a cyclopropyl group.
  • preferred examples of the compounds of Formula (XXV) may include compounds of Formula (V): [wherein R 1c represents a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or a cyclopropyl group, and R 2c represents -NH 2 or -NHOCH 3 ].
  • R 1c may have a substituent such as an alkyl group (e.g., a methyl group, an ethyl group, a propyl group, a butyl group), an alkoxy group (e.g., a methoxy group, an ethoxy group, a propoxy group, a butoxy group), an amino group, a hydroxyl group, a halogen atom or a silyl group.
  • an alkyl group e.g., a methyl group, an ethyl group, a propyl group, a butyl group
  • an alkoxy group e.g., a methoxy group, an ethoxy group, a propoxy group, a butoxy group
  • an amino group e.g., a hydroxyl group, a halogen atom or a silyl group.
  • Preferred examples of the compounds of Formula (XXV) may also include:
  • More preferred examples of the compounds of Formula (XXV) may include:
  • Even more preferred examples of the compounds of Formula (XXV) may include 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide (see Formula (XV)), and the most preferred example may be a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  • the compounds of Formula (XXV) can be prepared in a known manner, for example as described in International Publication No. WO02/03287 and/or International Publication No. WO2005/063713 .
  • the VEGF receptor kinase inhibitor may also preferably include compounds of Formula (XXVI): Formula (XXVI) is a preferred example of the compounds of Formula (XXIV).
  • R 11f represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C 1-6 alkylamino group.
  • R 11f include an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C 1-6 alkylamino group.
  • R 11f include any one group selected from those represented by the following formulae: which may have one or more substituents selected from the following substituent group:
  • R N1 and R N2 each independently represent a hydrogen atom or an optionally substituted C 1-6 alkyl group; and Me denotes a methyl group).
  • R 11f include any one group selected from those represented by the following formulae:
  • R 12f represents a hydrogen atom or an optionally substituted C 1-6 alkyl group.
  • R 12f include a hydrogen atom.
  • V f13 represents an oxygen atom or a sulfur atom.
  • V f13 include an oxygen atom.
  • a 11f represents an optionally substituted carbon atom or a nitrogen atom.
  • Preferred examples of A 11f include a carbon atom.
  • R 4f represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 2-7 acyl group or an optionally substituted C 2-7 alkoxycarbonyl group.
  • R 4f include a hydrogen atom.
  • R 5f represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group, an optionally substituted C 2-6 alkynyl group, an optionally substituted C 3-8 cycloalkyl group, an optionally substituted C 6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group.
  • R 5f include a C 1-6 alkyl group or a C 3-8 cycloalkyl group.
  • R 5f More preferred examples of R 5f include a methyl group.
  • R 9f represents a hydrogen atom, a halogen atom or an optionally substituted C 1-6 alkyl group.
  • R 9f include a hydrogen atom.
  • preferred examples of the compounds of Formula (XXVI) may include compounds of Formula (VI):
  • R 1d represents any one group selected from the group consisting of those represented by the following formulae: which may have one or more substituents selected from the substituent group ⁇
  • R 2d represents -NHR 3d (wherein R 3d represents a methyl group, an ethyl group or a cyclopropyl group), provided that the substituent group ⁇ denotes a group consisting of a hydroxyl group, a C 1-6 alkyl group, a C 3-8 cycloalkyl group, and groups represented by the following formulae: (wherein R N1' and R N2' each independently represent a hydrogen atom or a C 1-6 alkyl group).
  • R 3d may have a substituent such as an alkyl group (e.g., a methyl group, an ethyl group, a propyl group, a butyl group), an alkoxy group (e.g., a methoxy group, an ethoxy group, a propoxy group, a butoxy group), an amino group, a hydroxyl group, a halogen atom (e.g., fluorine, chlorine, bromine, iodine) or a silyl group.
  • substituents introduced into R N1' or R N2' may include the same substituents as mentioned above.
  • Preferred examples of the compounds of Formula (XXVI) may also include:
  • the compounds of Formula (XXVI) can be prepared in a known manner, for example as described in International Publication No. W02004/020434 .
  • the VEGF receptor kinase inhibitor may include, for example:
  • the VEGF receptor kinase inhibitor may also include:
  • SU14813, OSI930, TKI-28, ABP309, BAY 57-9352, BAY 43-9006, CHIR258, JNJ17029259, AEE-788, CEP-5214, KI-8751, VGA-1155, ABT-869, AG-028262, BMS-540215 and BMS-582664 can be prepared in a known manner, for example as described in the respective documents.
  • the VEGF receptor kinase inhibitor may also include, for example, BIBF1120 ( WO01/27081 ), ZK304709 ( Proceedings of the American Association for Cancer Research, 46, (Abstract 5842), 2005 ), Exel7647 ( EORTC-NCI-AACR Symp Mol Targets Cancer Ther., (Abstract 134), 2004 ), AMG706 ( EORTC-NCI-AACR Symp Mol Targets Cancer Ther., 2, (Abstract 151), 2004 ), GW-654652 ( Blood.,103, 3474-3479, 2004 , Proceedings of the American Association for Cancer Research, 44, 9, (Abstract 39), 2003 , Proceedings of the American Association for Cancer Research, 44, 9, (Abstract 40), 2003 ), and GW-786034 ( Proc.
  • BIBF1120 WO01/27081
  • ZK304709 Proceedings of the American Association for Cancer Research, 46, (Abstract 5842), 2005
  • BIBF1120, ZK304709, Exe17647, AMG706, GW-654652 and GW-786034 can be prepared in a known manner.
  • the VEGF receptor kinase inhibitor may further include, for example, anti-VEGF receptor antibodies.
  • Anti-VEGF receptor antibodies are those having affinity for the VEGF receptor or a fragment thereof. Such anti-VEGF receptor antibodies are preferably neutralizing antibodies that recognize and bind to the VEGF receptor to inhibit the vascular endothelial cell growth activity of VEGF.
  • the anti-VEGF receptor antibodies may be either polyclonal or monoclonal. Also, there is no particularly limitation on the isotypes of the antibodies.
  • the anti-VEGF receptor antibodies may also be either antibody fragments or single chain antibodies (see the section about anti-VEGF antibodies and anti-FGF antibodies described later).
  • the anti-VEGF receptor antibodies may preferably include 2C3 antibody ( US6524583 , US6676941 ), IMC-1121b ( US6811779 ), IMC-18F1 ( Proceedings of the American Association for Cancer Research, 45, 694, (Abstract 3005), 2004 ), IMC-1C11 ( US5747651 ), and IMC-2C6 ( Proceedings of the American Association for Cancer Research, 44, 1479, (Abstract 6454), 2003 ).
  • 2C3 antibody, IMC-1121b, IMC-18F1, IMC-1C11 and IMC-2C6 can be prepared in a known manner, for example as described in the respective documents.
  • preferred FGF receptor kinase inhibitors are 1-[2-amino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]-3-tert-butylurea (hereinafter also referred to as "PD166866"; J. M.
  • PD166866 J. M. C., 40, 2296-2303, 1997
  • PD173074 EMBO J., 17, 5896-5904, 1998
  • Compounds serving as VEGF receptor kinase inhibitors and compounds serving as FGF receptor kinase inhibitors may form pharmacologically acceptable salts with acids or bases.
  • the above receptor kinase inhibitors of the present invention also encompass these pharmacologically acceptable salts.
  • salts with acids include inorganic acid salts (e.g., hydrochloride salt, hydrobromide salt, sulfate salt, phosphate salt), as well as salts with organic acids such as formic acid, acetic acid, lactic acid, succinic acid, fumaric acid, maleic acid, citric acid, tartaric acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and trifluoroacetic acid.
  • inorganic acid salts e.g., hydrochloride salt, hydrobromide salt, sulfate salt, phosphate salt
  • organic acids such as formic acid, acetic acid, lactic acid, succinic acid, fumaric acid, maleic acid, citric acid, tartaric acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and trifluoro
  • salts with bases include alkali metal salts (e.g., sodium salt, potassium salt), alkaline earth metal salts (e.g., calcium salt, magnesium salt), salts with organic bases such as trimethylamine, triethylamine, pyridine, picoline, dicyclohexylamine, N,N'-dibenzylethylenediamine, arginine and lysine (organic amine salts), as well as ammonium salts.
  • alkali metal salts e.g., sodium salt, potassium salt
  • alkaline earth metal salts e.g., calcium salt, magnesium salt
  • salts with organic bases such as trimethylamine, triethylamine, pyridine, picoline, dicyclohexylamine, N,N'-dibenzylethylenediamine, arginine and lysine (organic amine salts), as well as ammonium salts.
  • compounds serving as VEGF receptor kinase inhibitors and compounds serving as FGF receptor kinase inhibitors may be in anhydride form or may form solvates such as hydrates.
  • Solvates may be either hydrates or anhydrates, preferably hydrates.
  • Solvents available for use include water, alcohols (e.g., methanol, ethanol, n-propanol) and dimethylformamide.
  • the VEGF receptor kinase inhibitors and FGF receptor kinase inhibitors according to the present invention also encompass their solvates and/or optical isomers.
  • the above receptor kinase inhibitors according to the present invention further encompass VEGF receptor kinase inhibitors and FGF receptor kinase inhibitors that are metabolized in vivo by oxidation, reduction, hydrolysis, conjugation, etc.
  • the above receptor kinase inhibitors according to the present invention encompass compounds that produce VEGF receptor kinase inhibitors and FGF receptor kinase inhibitors when metabolized in vivo by oxidation, reduction, hydrolysis, etc.
  • the anti-VEGF antibody is preferably a. neutralizing antibody that recognizes and binds to VEGF to inhibit the vascular endothelial cell growth activity of VEGF.
  • the anti-FGF antibody is preferably a neutralizing antibody that recognizes and binds to FGF to inhibit the fibroblast growth activity of FGF.
  • the anti-VEGF antibodies and anti-FGF antibodies may be either polyclonal or monoclonal. Also, there is no particularly limitation on the isotypes of these antibodies; the antibodies may have any isotype, for example, IgG (IgG 1 , IgG 2 , IgG 3 , IgG 4 ), IgM, IgA (IgA 1 , IgA 2 ), IgD or IgE.
  • Polyclonal and monoclonal antibodies can be prepared in a manner well known to those skilled in the art (Antibodies: A Laboratory Manual, E. Harlow and D. Lane, ed., Cold Spring Harbor Laboratory (Cold Spring Harbor, NY, 1988 )).
  • Polyclonal antibodies can be obtained, for example, by administering an antigen to a mammal (e.g., mouse, rabbit, rat), collecting the blood from the mammal, and separating and purifying antibody molecules from the collected blood.
  • Procedures for immunization are known to those skilled in the art and can be accomplished, e.g., by one or more administrations of an antigen.
  • an antigen including a part or all of VEGF or FGF
  • an adjuvant such as complete Freund's adjuvant or aluminum hydroxide, the use of an adjuvant may be eliminated depending on the route of administration or conditions, etc.
  • the blood may be collected from the mammal and then separated and purified in a routine manner, e.g., by centrifugation, precipitation with ammonium sulfate or polyethylene glycol; or various chromatographic techniques to obtain polyclonal antibodies in the form of a polyclonal antiserum.
  • the hybridoma method may be used for monoclonal antibody production.
  • a mammal is first immunized.
  • a part of the blood is preferably sampled and measured for its antibody titer in a known manner, e.g., by the ELISA method.
  • the spleen is then isolated from the sensitized and immunized animal to obtain B cells.
  • the B cells are then fused with myeloma cells in a routine manner to create antibody-producing hybridomas.
  • myeloma cells There is no particular limitation on the type of myeloma cells to be used and it is possible to use known types of myeloma cells.
  • any method known in the art such as the Sendai virus method, the polyethylene glycol method or the protoplast method, may be selected and used.
  • the resulting hybridomas are cultured in a routine manner in HAT medium (i.e., a medium containing hypoxanthine, aminopterin and thymidine) for an appropriate period of time to effect hybridoma selection. After screening to select a desired antibody-producing hybridoma, the hybridoma is cloned.
  • any method known for antibody detection such as the ELISA method or the radioimmunoassay method.
  • any method known in the art may be used, including the limiting dilution method and the FACS method.
  • the resulting hybridoma is cultured in an appropriate culture medium or is administered to a mammal (e.g., mouse peritoneal cavity) with which the hybridoma is compatible. From the culture solution or peritoneal fluid thus obtained, a desired monoclonal antibody can be isolated and purified by salting-out, ion exchange chromatography, gel filtration, affinity chromatography, etc.
  • Fragments and V region single chain antibodies of the above antibodies may also be used in the present invention.
  • Such antibody fragments mean partial regions of the above polyclonal or monoclonal antibodies. Specific examples include F(ab') 2 , Fab', Fab, Fv (variable fragment of antibody), sFv, dsFv (disulphide stabilized Fv) or dAb (single domain antibody).
  • the antibodies used in the present invention may also be humanized antibodies or human antibodies. Human antibodies can be created in the same manner as used for standard monoclonal antibody production, except for using a mammal whose immune system is replaced by the human immune system.
  • compositions, kits, method for cancer prevention/treatment, and method for angiogenesis inhibition are provided.
  • the present invention relates to pharmaceutical compositions, kits, a method for cancer prevention/treatment, and a method for angiogenesis inhibition, which are characterized in that a sulfonamide-including compound is combined with an angiogenesis inhibitor.
  • the sulfonamide-including compound is as described in "1.
  • Sulfonamide-including compounds may be at least one compound selected from (1) a compound of Formula (I), preferably LY186641 or LY295501, (2) a compound of Formula (II), preferably LY-ASAP, (3) LY573636 (Formula (III)), (4) CQS (Formula (IV), and (5) Formula (XIV), preferably E7070 or E7820.
  • the sulfonamide-including compound is more preferably at least one compound selected from LY295501 and LY573636, and particularly preferably a sodium salt of LY573636.
  • the sulfonamide-including compound is preferably E7070 or E7820.
  • angiogenesis inhibitor is as described in "2.
  • Angiogenesis inhibitors may be (a) a VEGF receptor kinase inhibitor, (b) an anti-VEGF antibody, (c) a FGF receptor kinase inhibitor or (d) an anti-FGF antibody.
  • the VEGF receptor kinase inhibitor (a) may be, for example, a compound represented by at least one selected from Formula (XXIV), Formula (XII), Formula (XIII), Formulae (XVI) to (XXM) and Formulae (XXVII) to (XXXIV).
  • the VEGF receptor kinase inhibitor (a) is preferably a compound of Formula (XXV) or (XXVI), more preferably a compound of Formula (V) or (VI), even more preferably 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide falling within the scope of Formula (V), and particularly preferably a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  • the VEGF receptor kinase inhibitor (a) is preferably a compound represented by at least one selected from Formula (XII), Formula (XIII), Formulae (XVI) to (XXIII) and Formulae (XXVII) to (XXXIV), and more preferably at least one compound selected from KRN951 (Formula (XIII)), AZD2171 (Formula (XIII)), AG013736 (Formula (XIII)), SU14813 (Formula (XVI)), OSI930 (Formula (XVII)), TKI-28 (Formula (XVIII)), ABP309 (Formula (XIX)), BAY 57-9352 (Formula (XX)), BAY 43-9006 (Formula (XXI)), CHIR258 (Formula (XXII)), JNJ17029259 (Formula (XXIII)), AEE-788 (Formula (XXVII), CHIR258 (
  • the FGF receptor kinase inhibitor (c) is preferably PD166866 or PD 173074.
  • the above compounds and angiogenesis inhibitors also encompass their pharmacologically acceptable salts or solvates (e.g., hydrates) thereof.
  • the sulfonamide compound and the angiogenesis inhibitor may be used in any combination of the above compounds and substances. Such a combination is not limited in any way and may include:
  • the pharmaceutical composition of the present invention comprises a sulfonamide-including compound in combination with an angiogenesis inhibitor.
  • the pharmaceutical composition of the present invention is useful as a pharmaceutical composition for cancer treatment and as a pharmaceutical composition for angiogenesis inhibition.
  • the pharmaceutical composition of the present invention is also provided as another embodiment, i.e., a pharmaceutical composition comprising a sulfonamide-including compound, which is administered together with an angiogenesis inhibitor to a patient.
  • the sulfonamide-including compound and the angiogenesis inhibitor may be administered simultaneously or separately.
  • the term “simultaneously” means that these components are administered at the same timing in a single administration schedule. In this case, it is not necessary to use completely the same hour and minute for administration.
  • the term “separately” means that these components are administered at different timings in a single administration schedule.
  • the phrase "in combination with” means a combination of compounds for combined use, and encompasses both modes in which separate compounds are administered in combination and as a mixture.
  • the kit of the present invention comprises a formulation comprising a sulfonamide-including compound and a formulation comprising an angiogenesis inhibitor.
  • the formulations contained in the kit of the present invention may be of any dosage form as long as they contain a sulfonamide-including compound or an angiogenesis inhibitor.
  • the kit of the present invention is useful as a kit for angiogenesis inhibition or as a kit for cancer treatment.
  • the pharmaceutical composition and/or kit of the present invention may further be combined with one or more additional anti-cancer agents.
  • additional anti-cancer agents are not limited in any way as long as they are formulations having an anti-cancer effect.
  • additional anti-cancer agents include, for example, irinotecan hydrochloride (CPT-11), oxaliplatin, 5-fluorouracil (5-FU), docetaxel (Taxotere ® ), gemcitabine hydrochloride (Gemzar ® ), calcium folinate (leucovorin), gefitinib (Iressa ® ), erlotinib (Tarceva ® ), and cetuximab (Erbitux ® ).
  • the above additional anti-cancer agents are particularly preferably irinotecan hydrochloride, oxaliplatin, 5-fluorouracil, calcium folinate, gefitinib, erlotinib and cetuximab in a case where the cancer type targeted by cancer therapeutic agent is colon cancer.
  • the above additional anti-cancer agents are particularly preferably gemcitabine hydrochloride, gefitinib, erlotinib and cetuximab for pancreas cancer, and gefitinib, erlotinib and cetuximab for renal cancer.
  • composition and/or kit of the present invention can be used as an angiogenesis inhibitory agent or as a cancer therapeutic agent.
  • cancer therapeutic agent is used to mean an anti-tumor agent, a cancer prognosis improver, a cancer recurrence inhibitor, a cancer metastasis inhibitor, etc.
  • the effect of cancer treatment may be confirmed by findings such as roentgenogram or CT analysis or histopathological diagnosis of biopsy specimens, or alternatively, by tumor marker levels.
  • the pharmaceutical composition and/or kit of the present invention may be administered to mammals (e.g., human, rat, rabbit, sheep, pig, cattle, cat, dog, monkey).
  • mammals e.g., human, rat, rabbit, sheep, pig, cattle, cat, dog, monkey.
  • the cancer type targeted by cancer therapeutic agent is not limited in any way, and examples include at least one selected from the group consisting of brain tumor, cervical cancer, esophageal cancer, tongue cancer, lung cancer, breast cancer, pancreas cancer, gastric cancer, large intestine cancer, small intestine cancer, duodenal cancer, colon cancer, rectal cancer, bladder cancer, renal cancer, liver cancer, prostate cancer, uterine cancer, ovarian cancer, thyroid gland cancer, gallbladder cancer, pharyngeal cancer, sarcoma (e.g., osteosarcoma, myosarcoma, fibrosarcoma) and melanoma.
  • sarcoma e.g., osteosarcoma, myosarcoma, fibrosarcoma
  • melanoma melanoma
  • administration may be conducted orally or parenterally.
  • the dose of the sulfonamide-including compound will vary depending on the severity of symptoms, the age, sex, body weight and differences in susceptibility of individual patients, the method of administration, the duration of administration, the interval of administration, the nature, pharmacy and type of individual pharmaceutical formulations, as well as the type of active ingredient, etc.
  • the daily dose for adults is usually 10 to 6000 mg, preferably 50 to 4000 mg, and more preferably 100 to 3000 mg, which may usually be given once to three times a day.
  • the daily adult dose of the VEGF receptor kinase inhibitor is usually 10 to 6000 mg, preferably 50 to 4000 mg, and more preferably 50 to 2000 mg, which may usually be given once to three times a day.
  • the daily adult dose of the FGF receptor kinase inhibitor is usually 10 to 6000 mg, preferably 50 to 4000 mg, and more preferably 50 to 2000 mg, which may usually be given once to three times a day.
  • the dose of the anti-VEGF antibody is usually 1 to 6000 mg, preferably 10 to 2000 mg, and more preferably 10 to 1000 mg, which may usually be given once to three times a day or a week.
  • the dose of the anti-FGF antibody is usually 1 to 6000 mg, preferably 10 to 2000 mg, and more preferably 10 to 1000 mg, which may usually be given once to three times a day or a week.
  • the amount of the sulfonamide-including compound to be used is not limited in any way and will vary depending on individual combinations with the VEGF receptor kinase inhibitor, anti-VEGF antibody, FGF receptor kinase inhibitor or anti-FGF antibody. For example, it is about a 0.01- to 100-fold excess (by weight), more preferably about a 0.1- to 10-fold excess (by weight), of the VEGF receptor kinase inhibitor, anti-VEGF antibody, FGF receptor kinase inhibitor or anti-FGF antibody.
  • compositions of the present invention may be formulated into various dosage forms, for example, oral solid formulations or parenteral formulations including injections, suppositories, ointments and cataplasm.
  • the sulfonamide-including compound and the angiogenesis inhibitor contained in the kit of the present invention may each be formulated into various dosage forms, for example, oral solid formulations or parenteral formulations including injections, suppositories, ointments and cataplasm.
  • these active ingredients may be supplemented with excipients and, if necessary, with binders, disintegrating agents, lubricants, coloring agents, flavoring agents and the like, followed by formulation in a routine manner into tablets, coated tablets, granules, fine granules, powders, capsules, etc. It is also possible to prepare oral non-solid formulations such as syrups, when needed.
  • excipients include lactose, corn starch, sucrose, glucose, sorbit, crystalline cellulose, and silicon dioxide.
  • binders include polyvinyl alcohol, ethylcellulose, methylcellulose, gum arabic, hydroxypropylcellulose, and hydroxypropylmethylcellulose.
  • lubricants include magnesium stearate, talc, and silica.
  • coloring agents include those permitted for use in pharmaceutical preparations.
  • flavoring agents include cocoa powder, menthol, aromatic acid, peppermint oil, borneol, and cinnamon powder.
  • tablets and granules may further be coated appropriately with sugar coating, gelatin coating or other coatings, if necessary.
  • these active ingredients may be supplemented, if necessary, with pH adjustors, buffers, suspending agents, solvent aids, stabilizing agents, isotonizing agents, preservatives and the like, followed by formulation in a routine manner into intravenous injections, subcutaneous injections, intramuscular injections, or intravenous drip infusions.
  • pH adjustors e.g., sodium bicarbonate
  • buffers e.g., sodium bicarbonate
  • solvent aids e.g., sodium bicarbonate
  • stabilizing agents e.g., sodium bicarbonate
  • isotonizing agents e.g., sodium bicarbonate
  • suspending agents may include methylcellulose, Polysorbate 80, hydroxyethylcellulose, gum arabic, powdered tragacanth, sodium carboxymethylcellulose, and polyoxyethylenesorbitan monolaurate.
  • solvent aids may include polyoxyethylene hydrogenated castor oil, Polysorbate 80, nicotinamide, polyoxyethylenesorbitan monolaurate, Macrogol, and an ethyl ester of castor oil fatty acid.
  • examples of stabilizing agents may include sodium sulfite, and sodium metasulfite.
  • examples of preservatives may include methyl parahydroxybenzoate, ethyl parahydroxybenzoate, sorbic acid, phenol, cresol, and chlorocresol.
  • the formulation comprising a sulfonamide-including compound and the formulation comprising an angiogenesis inhibitor may be mixed together or may be included in separate containers and packaged in a single package. These formulations may be administered either simultaneously or sequentially.
  • the kit of the present invention can be used as a kit for angiogenesis inhibition or as a kit for cancer treatment and further comprises a packaging container, an instruction manual, an package insert and the like, in addition to the formulation comprising a sulfonamide-including compound and the formulation comprising an angiogenesis inhibitor.
  • These packaging container, instruction manual and package insert may describe a combination for combined use of the formulations or may describe a dosage regimen for administration of separate formulations in combination or as a mixture, etc. Such a dosage regimen may be described by reference to the above description.
  • the kit of the present invention may comprise (a) at least one selected from the group consisting of a packaging container, an instruction manual and an package insert, each of which describes the combined use of a sulfonamide-including compound and an angiogenesis inhibitor, and (b) a pharmaceutical composition comprising the sulfonamide-including compound.
  • the kit is useful as a kit for cancer treatment or as a kit for angiogenesis inhibition.
  • the above pharmaceutical composition comprising the sulfonamide-including compound is useful as a pharmaceutical composition for cancer treatment and as a pharmaceutical composition for angiogenesis inhibition.
  • packaging container, instruction manual and package insert may describe the combined use of the sulfonamide-including compound and the angiogenesis inhibitor or may describe a dosage regimen for administration of separate substances in combination or as a mixture, etc. Such a dosage regimen may be determined by reference to the above description about the pharmaceutical composition/kit.
  • the present invention also includes the use of a sulfonamide-including compound for the manufacture of a pharmaceutical composition in combination with an angiogenesis inhibitor.
  • the above pharmaceutical composition is useful as a pharmaceutical composition for cancer treatment and as a pharmaceutical composition for angiogenesis inhibition.
  • the present invention also includes a method for preventing or treating cancer or a method for inhibiting angiogenesis, which comprises simultaneously or separately administering a sulfonamide-including compound and an angiogenesis inhibitor to a patient.
  • a method for preventing or treating cancer there is no particular limitation on the route and method of administration of the sulfonamide-including compound and the angiogenesis inhibitor.
  • the route and method of administration reference may be made to the above description about the pharmaceutical composition of the present invention.
  • the human colon cancer cell line HCT116 American Type Culture Collection, Manassas, VA, U.S.A.
  • the human leukemia cell line MOLT-4 American Type Culture Collection, Manassas, VA, U.S.A.
  • HCT116 cells and MOLT-4 cells were seeded at a density of 2.0 ⁇ 10 6 cells into cell culture dishes of 10 cm diameter and cultured for 24 hours, followed by compound treatment as shown below.
  • E7820 (0.8 ⁇ M), E7070 (0.8 ⁇ M), LY295501 (30 ⁇ M), CQS (8 ⁇ M), adriamycin (0.2 ⁇ M), daunomycin (0.2 ⁇ M), ICRF154 (80 ⁇ M), ICRF159 (80 ⁇ M), kenpaullone (10 ⁇ M), alsterpullone (10 ⁇ M), trichostatin A (0.1 ⁇ M) and rapamycin (80 ⁇ M).
  • E7070 (0.8 ⁇ M) was evaluated.
  • adriamycin and daunomycin are known as DNA topoisomerase II inhibitors of DNA intercalation type
  • ICRF154 and ICRF159 are known as DNA topoisomerase II inhibitors of catalytic type
  • kenpaullone and alsterpullone are known as cyclin-dependent kinases (CDKs) inhibitors
  • trichostatin A is known as a histone deacetylase inhibitor
  • rapamycin is known as a mTOR/FRAP inhibitor.
  • the treatment concentration of each compound was set to a concentration three to five times higher than the 50% growth inhibitory concentration of each compound against HCT116 cells (based on 3-day cell growth inhibition assays using WST-8). After treatment for 24 hours at the set concentration in parentheses following the name of each compound, the cells were collected. Moreover, the cells cultured for 24 hours in the absence of these compounds were also collected.
  • RNA extraction of total RNA from the collected cells was performed using a TRIZOL reagent (Invitrogen Corporation) according to the instructions attached thereto.
  • RNA was dissolved in 100 ⁇ l of diethyl pyrocarbonate (DEPC)-treated sterilized water and further purified using an RNeasy column (QIAGEN), followed by synthesis of double-stranded cDNA using a SuperScript Choice System (Invitrogen Corporation) and a T7-d(T) 24 primer.
  • DEPC diethyl pyrocarbonate
  • QIAGEN RNeasy column
  • RNA was supplemented with 5 ⁇ M T7-d(T) 24 primer, 1x First strand buffer, 10 mM DTT, 500 ⁇ M dNTP mix and 20 units/ ⁇ l SuperScript II Reverse Transcriptase, and then reacted at 42°C for 1 hour to synthesize single-stranded DNA.
  • 1x Second strand buffer, 200 ⁇ M dNTP mix, 67 U/ml DNA ligase, 270 U/ml DNA polymerase I and 13 U/ml RNase H were added and reacted at 16°C for 2 hours to synthesize double-stranded cDNA.
  • 67 U/ml T4 DNA polymerase I was added and reacted at 16°C for 5 minutes, followed by addition of 10 ⁇ l of 0.5 M EDTA to stop the reaction.
  • the resulting cDNA was purified by phenol/chloroform and labeled with biotinylated UTP and CTP using an RNA Transcript Labeling Kit (Enzo Diagnostics) according to the instructions attached thereto.
  • the reaction product was purified on an RNeasy column and then heated in 200 mM trisacetic acid pH 8.1, 150 mM magnesium acetate, 50 mM potassium acetate at 94°C for 35 minutes to fragment cRNA.
  • the fragmented cRNA was hybridized to a GeneChip (Affymetrix) Human Focus array in 100 mM MES, 1 M sodium salt, 20 mM EDTA, 0.01% Tween 20 at 45°C for 16 hours. After hybridization, the GeneChip was washed and stained according to the protocol Midi_euk2 attached to an Affymetrix fluidics station. The staining was accomplished by using streptavidin-phycoerythrin and a biotinylated anti-streptavidin goat antibody. The stained GeneChip was scanned with an HP argon ion laser confocal microscope (Hewlett Packard) and measured for fluorescence intensity. The measurement was performed with an excitation wavelength of 488 nm and an emission wavelength of 570 nm.
  • Figure 1 shows the results of hierarchical clustering analysis performed on HCT116 cells.
  • HCT116 cells were used to study changes in gene expression induced by treatment with the following 12 compounds: E7820 (0.16 ⁇ M), E7070 (0.26 ⁇ M), LY186641 (59 ⁇ M), LY295501 (24 ⁇ M), LY573636 (9.6 ⁇ M), CQS (4.0 ⁇ M), MST16 (100 ⁇ M), etoposide (3.6 ⁇ M), ethoxzolamide (410 ⁇ M), capsaicin (280 ⁇ M), trichostatin A (0.16 ⁇ M) and kenpaullone (7.1 ⁇ M).
  • MST16 is known as a DNA topoisomerase II inhibitor of catalytic type
  • etoposide is known as a DNA topoisomerase II inhibitor inducing cleavable complex formation
  • ethoxzolamide is known as a carbonic anhydrase inhibitor
  • capsaicin is known as a tumor-specific plasma membrane NADH oxidase inhibitor
  • trichostatin A is known as a histone deacetylase inhibitor
  • kenpaullone is known as a cyclin-dependent kinases (CDKs) inhibitor.
  • CDKs cyclin-dependent kinases
  • the treatment concentration of each compound was set to a concentration twice higher than the 50% growth inhibitory concentration of each compound against HCT116 cells (based on 3-day cell growth inhibition assays using MTT). After treatment for 24 hours at the set concentration in parentheses following the name of each compound, the cells were collected. Moreover, the cells cultured for 24 hours in the absence of these compounds were also collected.
  • the 26 .cel files obtained in this example for 13 samples (Control + 12 compounds) in duplicate were normalized at the probe level by applying the RMA (robust multi-array average) method ( Biostatistics (2003), 4, 249-264 ), followed by calculating the log value of signal intensity at the gene level. Subsequently, the log value of signal intensity in the untreated group (Control-1) was subtracted from the log value of signal intensity in each compound-treated group for each gene to obtain the log signal ratio of each compound-treated group to Control-1. The cosine correlation coefficient was then calculated and defined as a correlation coefficient between experiments ( Figure 2). Based on this correlation coefficient, hierarchical clustering analysis was performed by the UPGMA (Unweighted Pair Group Method with Arithmetic mean) method ( Figure 3). The same calculation was also performed on Control-2 ( Figures 4 and 5). The software programs used were R 2.0.1 (http://www.r-project.org/) and affy package 1.5.8 (http://www.bioconductor.org).
  • LY1 denotes LY186641
  • LY2 denotes LY295501
  • LY5 denotes LY573636
  • CAI denotes ethoxzolamide
  • Cap denotes capsaicin
  • MST denotes MST16
  • Etop denotes etoposide
  • TSA trichostatin A
  • Kenp denotes kenpaullone.
  • de hclust (*, "average) is a command for statistical analysis and means that the average of duplicate experimental data was used for clustering analysis in R.
  • Panels of 36 human cancer cell lines were used to study the correlation of antiproliferative activity among E7820, E7070, CQS, LY186641 and LY295501.
  • the cancer cell lines used were the following 36 lines: DLD-1, HCT15, HCT116, HT29, SW480, SW620 and WiDr (human colon cancer cell lines), A427, A549, LX-1, NCI-H460, NCI-H522, PC-9 and PC-10 (human lung cancer cell lines), GT3TKB, HGC27; MKN1, MKN7, MKN28 and MKN74 (human stomach cancer cell lines), AsPC-1, KP-1, KP-4, MiaPaCaII, PANC-1 and SUIT-2 (human pancreas cancer cell lines), BSY-1, HBC5, MCF-7, MAD-MB-231, MDA-MB-435 and MDA-MB-468 (human breast cancer cell lines), as well as CCRF-CEM, HL60, K562
  • Table 1 shows the type, initial cell number and doubling time of human cancer cell lines in human cancer cell line panels.
  • HCT116-C9 was a sub-clone separated from the human colon cancer cell line HCT116 (American Type Culture Collection, Manassas, VA, U.S.A.), while HCT116-C9-C1 and HCT116-C9-C4 were E7070-resistant sub-clonal cell lines obtained by culturing this HCT116-C9 in the presence of gradually increasing concentrations of E7070 ( Molecular Cancer Therapeutics, 2002, 1, 275-286 ).
  • HCT116-C9, HCT116-C9-C1 and HCT116-C9-C4 were each seeded at 3000 cells/well in 96-well microplates (flat-bottomed) (50 ⁇ l/well). After 24 hours, a 3-fold dilution series of each compound was added (50 ⁇ l/well). After 72 hours, the cell growth inhibitory activity was evaluated by the MTT method ( Mossmann T., J. Immunol. Methods, 1983, 65, 55-63 ). The least squares method was used to determine the 50% growth inhibitory concentration of each compound against each cancer cell line.
  • IC50 0.080 ⁇ M, 1.73 ⁇ M, 33.6 ⁇ M, 10.9 ⁇ M and 1.63 ⁇ M, respectively
  • Example 4 Exactly the same procedure as used in Example 4 was repeated to evaluate the antiproliferative activity of both LY573636 and E7070 using E7070-resistant sub-clonal cell lines.
  • E7820 has been found to show excellent angiogenesis inhibitory activity and anti-tumor activity when used in combination with an angiogenesis inhibitory agent (see WO03/074045 ).
  • a sulfonamide-including compound preferably E7070, LY186641, LY295501, LY-ASAP, LY573636 or CQS or combinations thereof, showed excellent angiogenesis inhibitory activity and anti-tumor activity when used in combination with an angiogenesis inhibitor.
  • Example 6 Combined use of E7820 and 4-(3-chloro-4-(cyclopropylaminocarbonyl)-aminophenoxy)-7-methoxy-6-quinolinecarboxamide in subcutaneous transplantation model ( in vivo ) of human renal cancer cell line 786-O
  • Human renal cancer cell line 786-O (purchased from ATCC) was cultured in RPMI1640 (containing 10% FBS) to about 80% confluency in a 5% carbon dioxide incubator, and the cells were collected by trypsin-EDTA. The cells were diluted with 50% Matrigel-containing phosphate buffer to prepare a 1 ⁇ 10 8 cells/mL suspension, and the resulting cell suspension was subcutaneously transplanted in 0.1 mL volumes to nude mice at the side of their body.
  • Tumor long and short axes were measured with a digimatic caliper (Mitsutoyo) and used to calculate both tumor volume and relative tumor volume according to the following equations.
  • Tumor volume TV tumor long axis mm ⁇ tumor short axis 2 mm 2 / 2
  • E7820 was found to produce a synergistic effect when used in combination with 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, and their combined use showed an excellent anti-tumor effect when compared to the effect of E7820 or 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide alone (Table 3 and Figure 8).
  • Table 3 Analyte administered Relative tumor volume at Day 22 Mean ⁇ SD Two-way ANOVA Control (untreated) 1.61 ⁇ 0.23 E7820 100 mg/kg 0.80 ⁇ 0.13 Compound A 100 mg/kg 0.59 ⁇ 0.12 E7820 100 mg/kg + Compound A 100 mg/kg 0.16 ⁇ 0.02 p ⁇ 0.01 Synergistic effect Table 3 shows the anti-tumor effect produced by either one or a combination ofE7820 and 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide (in Table 3 and Figure 8, Compound A denotes 4-(3-chloro-4-(cyclopropylaminocarbonyl)-aminophenoxy)-7-methoxy-6-quinolinecarboxamide) in the transplantation model ( in vivo ) of renal cancer cell line 786-O. The first day of administration was defined as Day 1.
  • a combination of E7820 and 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide provides pharmaceutical compositions and kits showing excellent anti-tumor activity; the pharmaceutical compositions and kits of the present invention can be used for cancer treatment.
  • the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity.
  • the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity.
  • the pharmaceutical compositions and kits of the present invention are useful for cancer treatment or angiogenesis inhibition.
  • the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity.
  • the pharmaceutical compositions and kits of the present invention are useful for cancer treatment or angiogenesis inhibition.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention relates to pharmaceutical compositions comprising a sulfonamide-including compound in combination with an angiogenesis inhibitor.

Description

    FIELD OF THE INVENTION
  • The present invention relates to novel pharmaceutical, compositions and kits, which are characterized by comprising a sulfonamide-including compound in combination with an angiogenesis inhibitor, more specifically with a VEGF inhibitor or a FGF inhibitor.
    • BACKGROUND ART
  • Cancer chemotherapeutics conventionally used include alkylating agents such as cyclophosphamide, antimetabolites such as methotrexate and fluorouracil, antibiotics such as adriamycin, mitomycin and bleomycin, plant-derived agents such as taxol, vincristine and etoposide, as well as metal complexes such as cisplatin. However, none of these substances can be regarded as having a sufficient anti-tumor effect; there has been a strong demand for the development of new anti-tumor agents.
  • In recent years, sulfonamide-including compounds have been reported as useful anti-tumor agents(1-4). Among them, N-(3-chloro-1H-indol-7-yl)-4-sulfamoylbenzenesulfonamide (hereinafter also referred to as E7070), N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide (hereinafter also referred to as E7820), N-[[(4-chlorophenyl)-amino]carbonyl]-2,3-dihydro-1H-indene-5-sulfonamide (hereinafter also referred to as LY186641), N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide (hereinafter also referred to as LY295501), N-(2,4-dichlorobenzoyl)-4-chlorophenyl-sulfonamide (hereinafter also referred to as LY-ASAP), N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide (hereinafter also referred to as LY573636), 2-sulfanylamido-5-chloroquinoxaline (hereinafter also referred to as CQS) and the like have been found to be active against various types of tumors and hence very useful.
  • Previous studies have reported that the combined use of E7820 which is one of the sulfonamide-including compounds and an angiogenesis inhibitor produces excellent angiogenesis inhibitory activity and anti-tumor activity(5).
  • In recent years, methods have been established for simultaneously detecting the expression levels of many genes using various DNA microarrays, which are applied to a wide range of purposes(6-7). Likewise, several reports have been made on studies in which DNA microarrays (In part, there is macroarray which uses membrane filters) are used to detect changes in gene expression caused when tumor cells are treated with anti-cancer agents(8-10). These reports indicate that the analysis of gene expression changes is very useful in comprehensively studying, at the molecular level, property comparison of a plurality of cell populations and biological changes in cells caused by treatment with drugs, etc.
  • In addition, there are other reports in which a panel of 60 cancer cell lines from the US National Cancer Institute is reclassified and examined for their properties based on the analysis of their gene expression profiles(11) and in which the panel of 60 cancer cell lines is further studied for the relationship between their gene expression profiles and the susceptibility of each cell line to various anti-cancer agents(12).
    • References
    1. (1) JP 7-165708 A
    2. (2) International Publication No. WO00/50395
    3. (3) European Patent Publication No. 0222475
    4. (4) International Publication No. WO02/098848
    5. (5) International Publication No. WO03/074045
    6. (6) Schena M, Shalon D, Davis RW, Brown PO. Science, 1995, 270, 467-70.
    7. (7) Lockhart, D.J., Dong, H., Byrne, M.C., Follettie, M.T., Gallo, M.V, Chee, M.S., Mittmann, M., Wang C., Kobayashi, M., Horton, H. Brown, E.L., Nature Biotechnology, 1996, 14, 1675-1680.
    8. (8) Rhee CH, Ruan S, Chen S, Chenchik A, Levin VA, Yung AW, Fuller GN, Zhang W, Oncol Rep, 1999, 6, 393-401.
    9. (9) Zimmermann J, Erdmann D, Lalande I, Grossenbacher R, Noorani M, Furst P, Oncogene, 2000, 19, 2913-20.
    10. (10) Kudoh K, Ramanna M, Ravatn R, Elkahloun AG Bittner ML, Meltzer PS, Trent JM, Dalton WS, Chin KV, Cancer Res, 2000, 4161-6.
    11. (11) Ross DT, Scherf U, Eisen MB, Perou CM, Rees C, Spellman P, Iyer V, Jeffrey SS, Van de Rijn M, Waltham M, Pergamenschikov A, Lee JC, Lashkari D, Shalon D, Myers TG, Weinstein JN, Botstein D, Brown PO, Nat Genet, 2000, 24, 227-35.
    12. (12) Scherf U, Ross DT, Waltham M, Smith LH, Lee JK, Tanabe L, Kohn KW, Reinhold WC, Myers TG Andrews DT, Scudiero DA, Eisen MB, Sausville EA, Pommier Y, Botstein D, Brown PO, Weinstein JN, Nat Genet, 2000, 24, 236-44.
    SUMMARY OF THE INVENTION
  • The present invention was made under such circumstances, and the problem to be solved by the invention is to find out pharmaceutical compositions and kits having excellent angiogenesis inhibitory activity and/or anti-tumor activity.
  • As a result of extensive and intensive efforts made to solve the problem stated above, the inventors of the present invention have found that there is a high correlation between the pattern of gene expression changes and cell growth inhibitory activity provided by E7820, E7070, LY186641, LY295501, LY573636 or CQS or combinations thereof in experiments using DNA microarrays and cancer cell line panels. Likewise, in cell growth inhibition assays, the inventors have also found that cancer cell lines resistant to E7070 have cross-resistance to E7820, LY186641, LY295501, LY ASAP, LY573636 and CQS. Based on these results, the inventors of the present invention have obtained a finding that E7070, E7820, LY186641, LY295501, LY-ASAP, LY573636 or CQS or combinations thereof have the same or similar mechanism of action and produce the same or similar genetic changes and effects.
  • On the other hand, E7820 has been reported to show excellent angiogenesis inhibitory activity and anti-tumor activity when used in combination with an angiogenesis inhibitor ( WO03/074045 ). Thus, based on the above finding, E7070, LY186641, LY295501, LY-ASAP, LY573636 or CQS or combinations thereof are also believed to show excellent angiogenesis inhibitory activity and anti-tumor activity when used in combination with an angiogenesis inhibitor; sulfonamide-including compounds, preferably E7070, LY186641, LY295501, LY-ASAP, LY573636 or CQS or combinations thereof, have now been found to provide useful pharmaceutical compositions and kits when combined with angiogenesis inhibitors.
  • Namely, the present invention is directed to the following.
    1. (1) A pharmaceutical composition comprising a sulfonamide-including compound in combination with an angiogenesis inhibitor.
    2. (2) A kit comprising:
      1. (a) at least one selected from the group consisting of a packaging container, an instruction manual and an package insert, each of which describes the combined use of a sulfonamide-including compound and an angiogenesis inhibitor; and
      2. (b) a pharmaceutical composition comprising the sulfonamide-including compound.
    3. (3) A kit comprising a set of a formulation comprising a sulfonamide-including compound and a formulation comprising an angiogenesis inhibitor.
    4. (4) A method for preventing or treating cancer and/or a method for inhibiting angiogenesis, which comprises administering a sulfonamide-including compound and an angiogenesis inhibitor to a patient.
    5. (5) Use of a sulfonamide-including compound for the manufacture of a pharmaceutical composition in combination with an angiogenesis inhibitor.
    6. (6) A pharmaceutical composition comprising a sulfonamide-including compound, which is administered together with an angiogenesis inhibitor to a patient.
  • The above sulfonamide-including compound includes at least one compound selected from the group consisting of
    • a compound of Formula (I):
      Figure imgb0001
    [wherein E represents -O-, -N(CH3)-, -CH2-, -CH2CH2- or -CH2O-, D represents -CH2- or -O-, R1a represents a hydrogen atom or a halogen atom, and R2a represents a halogen atom or a trifluoromethyl group],
    a compound of Formula (II):
    Figure imgb0002
     [wherein J represents -O- or -NH-, R1b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted C1-4 alkylthio group, an optionally substituted C2-5 alkoxycarbonyl group, a nitro group, an azido group, -O(SO2)CH3, -N(CH3)2, a hydroxyl group, a phenyl group, a substituted phenyl group, a pyridinyl group, a thienyl group, a furyl group, a quinolinyl group or a triazole group, R2b represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-5 alkoxycarbonyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted phenyl group or an optionally substituted quinolinyl group, R3b represents a hydrogen atom or an optionally substituted C1-4 alkoxy group, R4b represents a hydrogen atom or an optionally substituted C1-6 alkyl group (provided that at least one of R3b and R4b is a hydrogen atom), R5b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group or a nitro group, R6b represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group (provided that when R6b is an optionally substituted C1-6 alkyl group, R5b is a hydrogen atom and R7b is a halogen atom), and R7b represents a halogen atom or an optionally substituted C1-6 alkyl group (provided that when either R5b or R7b is an optionally substituted C1-6 alkyl group or when R7b is a halogen atom or an optionally substituted C1-6 alkyl group, either R5b or R6b is a hydrogen atom)],
    a compound of Formula (III):
    Figure imgb0003
     and
    a compound of Formula (IV):
    Figure imgb0004
     or a pharmacologically acceptable salt thereof or a solvate thereof.
  • Alternatively, the above sulfonamide-including compound may be a compound of Formula (IX):
    Figure imgb0005
     or a pharmacologically acceptable salt thereof or a solvate thereof
  • The present invention is also directed to the following.
    • (7) A pharmaceutical composition comprising a sulfonamide-including compound in combination with a VEGF receptor kinase inhibitor.
    • (8) A kit comprising:
      1. (a) at least one selected from the group consisting of a packaging container, an instruction manual and an package insert, each of which describes the combined use of a sulfonamide-including compound and a VEGF receptor kinase inhibitor; and
      2. (b) a pharmaceutical composition comprising the sulfonamide-including compound.
    • (9) A kit comprising a set of a formulation comprising a sulfonamide-including compound and a formulation comprising a VEGF receptor kinase inhibitor.
    • (10) A method for preventing or treating cancer and/or a method for inhibiting angiogenesis, which comprises administering a sulfonamide-including compound and a VEGF receptor kinase inhibitor to a patient.
    • (11) Use of a sulfonamide-including compound for the manufacture of a pharmaceutical composition in combination with a VEGF receptor kinase inhibitor.
    • (12) A pharmaceutical composition comprising a sulfonamide-including compound, which is administered together with a VEGF receptor kinase inhibitor.
  • The above sulfonamide-including compound includes a compound of Formula (XIV):
    Figure imgb0006
     [wherein
    • the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    • the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    • the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    • W represents a single bond or -CH=CH-,
    • X represents -N(R1)- or an oxygen atom,
    • Y represents:
      Figure imgb0007
       and
    • Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group]
    or a pharmacologically acceptable salt thereof or a solvate thereof
  • The above VEGF receptor kinase inhibitor may include at least one compound selected from the group consisting of:
    • (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    • (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    • (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    • (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    • (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    • (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    • (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    • (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    • (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    • (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    • (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    • (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    • (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    • (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    • (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    • (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    • (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    • (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    • (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methy)pyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate
    or a pharmacologically acceptable salt thereof or a solvate thereof
  • Alternatively, the above VEGF receptor kinase inhibitor may be 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  • The present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity.
  • More specifically, as a result of combining sulfonamide-including compounds, preferably E7070, LY186641, LY295501, LY-ASAP, LY573636 or CQS or combinations thereof, with angiogenesis inhibitors, the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity and enables them to be used for cancer treatment or angiogenesis inhibition. Likewise, when combining sulfonamide-including compounds, preferably E7820, with VEGF receptor kinase inhibitors, the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity and enables them to be used for cancer treatment or angiogenesis inhibition.
    • BRIEF DESCRIPTION OF THE DRAWINGS
    • Figure 1 shows the results of hierarchical clustering analysis in DNA microarrays in Example 1.
    • Figure 2 shows correlation coefficients in DNA microarrays in Example 2.
    • Figure 3 shows the results of hierarchical clustering analysis in DNA microarrays in Example 2.
    • Figure 4 shows correlation coefficients in DNA microarrays in Example 2.
    • Figure 5 shows the results of hierarchical clustering analysis in DNA microarrays in Example 2.
    • Figure 6 shows the antiproliferative effect of E7070, E7820, CQS, LY186641, LY295501 and LY-ASAP on HCT 116-C9, HCT116-C9-C1 and HCT 116-C9-C4, as measured by cell growth inhibition assay.
    • Figure 7 shows the antiproliferative effect of E7070 and LY573636 on HCT116-C9, HCT116-C9-C1 and HCT116-C9-C4, as measured by cell growth inhibition assay.
    • Figure 8 shows the combined effect of E7820 and 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide on tumor growth in a subcutaneous transplantation model (in vivo) of human renal cancer cell line 786-O. In Figure 8, Compound A denotes 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
    DETAILED DESCRIPTION OF THE INVENTION
  • Embodiments of the present invention will be explained below. The following embodiments are provided for illustrative purposes only, and are not intended to limit the scope of the invention. The present invention can be embodied in various forms without departing from the spirit of the invention.
  • All documents cited herein, including journal articles, patent gazettes and other patent documents, are incorporated herein by reference.
  • As used herein, the term "halogen atom" refers to a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
  • As used herein, the term "C1-6 alkyl group" refers to a linear or branched alkyl group containing 1 to 6 carbon atoms. Specific examples include a methyl group, an ethyl group, a 1-propyl group (i.e., a n-propyl group), a 2-propyl group (i.e., an i(iso)-propyl group or an isopropyl group), a 2-methyl-1-propyl group (i.e., an i-butyl group or an isobutyl group), a 2-methyl-2-propyl group (i.e., a t(tert)-butyl group), a 1-butyl group (i.e., a n-butyl group), a 2-butyl group (i.e., a s(sec)-butyl group), a 1-pentyl group (i.e., a n-pentyl group or an amyl group), a 2-pentyl group (i.e., a 1-methylbutyl group), a 3-pentyl group (i.e., a 1-ethylpropyl group), a 2-methyl-1-butyl group (i.e., a 2-methylbutyl group), a 3-methyl-1-butyl group (i.e., an isopentyl group), a 2-methyl-2-butyl group (i.e., a t(tert)-pentyl group), a 3-methyl-2-butyl group (i.e., a 1,2-dimethylpropyl group), a 2,2-dimethyl-1-propyl group (i.e., a neopentyl group), a 1-hexyl group (i.e., a n-hexyl group), a 2-hexyl group (i.e., a 1-methylpentyl group), a 3-hexyl group (i.e., a I-ethylbutyl group), a 2-methyl-1-pentyl group (i.e., a 2-methylpentyl group), a 3-methyl-l-pentyl group (i.e., a 3-methylpentyl group), a 4-methyl-1-pentyl group (i.e., an isohexyl group), a 2-methyl-2-pentyl group (i.e., a 1,1-dimethylbutyl group), a 3-methyl-2-pentyl group (i.e., a 1,2-dimethylbutyl group), a 4-methyl-2-pentyl group (i.e., a 1,3-dimethylbutyl group), a 2-methyl-3-pentyl group (i.e., a 1-ethyl-2-methylpropyl group), a 3-methyl-3-pentyl group (i.e., a 1-ethyl-1-methylpropyl group), a 2,3-dimethyl-butyl group (i.e., a 2,3-dimethylbutyl group), a 3,3-dimethyl-1-butyl group (i.e., a 3,3-dimethylbutyl group), a 2,2-dimethyl-1-butyl group (i.e., a 2,2-dimethylbutyl group), a 2-ethyl-1-butyl group (i.e., a 2-ethylbutyl group), a 3,3-dimethyl-2-butyl group (i.e., a 1,2,2-trimethylpropyl group), and a 2,3-dimethyl-2-butyl group (i.e., a 1,1,2-trimethylpropyl group).
  • Preferred examples of the "C1-6 alkyl group" may include a methyl group, an ethyl group, a 1-propyl group, a 2-propyl group, a 2-methyl-1-propyl group, a 2-methyl-2-propyl group, a 1-butyl group, and a 2-butyl group.
  • As used herein, the term "C1-6 alkylene group" refers to a divalent group derived by removing any one hydrogen atom from the "C1-6 alkyl group" defined above. Specific examples include a methylene group, a 1,2-ethylene group, a 1,1-ethylene group, a 1,3-propylene group, a tetramethylene group, a pentamethylene group, and a hexamethylene group.
  • As used herein, the term "C2-6 alkenyl group" refers to a linear or branched alkenyl group having one double bond and containing 2 to 6 carbon atoms. Specific examples include an ethenyl group (i.e., a vinyl group), a 1-propenyl group, a 2-propenyl group (i.e., an allyl group), a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a pentenyl group, and a hexenyl group.
  • As used herein, the term "C2-6 alkynyl group" refers to a linear or branched alkynyl group having one triple bond and containing 2 to 6 carbon atoms. Specific examples include an ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, a pentynyl group, and a hexynyl group.
  • As used herein, the term "C3-8 cycloalkyl group" refers to a monocyclic or bicyclic saturated aliphatic hydrocarbon group containing 3 to 8 carbon atoms. Specific examples include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, a bicyclo[2.1.0]pentyl group, a bicyclo[3.1.0]hexyl group, a bicyclo[2.1.1]hexyl group, a bicyclo[4.1.0]heptyl group, a bicyclo[2.2.1]heptyl group (i.e., a norbornyl group), a bicyclo[3.3.0]octyl group, a bicyclo[3.2.1]octyl group, and a bicyclo[2.2.2]octyl group.
  • Preferred examples of the "C3-8 cycloalkyl group" may include a cyclopropyl group, a cyclobutyl group, and a cyclopentyl group.
  • As used herein, the term "C6-10 aryl group" refers to an aromatic cyclic hydrocarbon group containing 6 to 10 carbon atoms. Specific examples include a phenyl group, a 1-naphthyl group, a 2-naphthyl group, an indenyl group, and an azulenyl group.
  • Preferred examples of the "C6-10 aryl group" may include a phenyl group.
  • As used herein, the term "heteroatom" refers to a nitrogen atom, an oxygen atom or a sulfur atom.
  • As used herein, the term "5- to 10-membered heteroaryl group" refers to an aromatic cyclic group having 5 to 10 ring member atoms, 1 to 5 of which are heteroatoms. Specific examples include a furyl group, a thienyl group, a pyrrolyl group, an imidazolyl group, a triazolyl group, a tetrazolyl group, a thiazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, an isothiazolyl group, a furazanyl group, a thiadiazolyl group, an oxadiazolyl group, a pyridyl group, a pyrazinyl group, a pyridazinyl group, a pyrimidinyl group, a triazinyl group, a purinyl group, a pteridinyl group, a quinolyl group, an isoquinolyl group, a naphthylizinyl group, a quinoxalinyl group, a cinnolinyl group, a quinazolinyl group, a phthalazinyl group, an imidazopyridyl group, an imidazothiazolyl group, an imidazooxazolyl group, a benzothiazolyl group, a benzoxazolyl group, a benzimidazolyl group, an indolyl group, an isoindolyl group, an indazolyl group, a pyrrolopyridyl group, a thienopyridyl group, a furopyridyl group, a benzothiadiazolyl group, a benzooxadiazolyl group, a pyridopyrimidinyl group, a benzofuryl group, a benzothienyl group, and a thienofuryl group.
  • Preferred examples of the "5- to 10-membered heteroaryl group" may include a furyl group, a thienyl group, a pyrrolyl group, an imidazolyl group, a thiazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, an isothiazolyl group, a pyridyl group, and a pyrimidinyl group.
  • As used herein, the term "3- to 10-membered non-aromatic heterocyclic group" refers to a non-aromatic cyclic group characterized by:
    1. (1) having 3 to 10 ring member atoms;
    2. (2) containing 1 or 2 heteroatoms as the ring member atoms;
    3. (3) optionally containing 1 or 2 double bonds in the ring;
    4. (4) optionally containing 1 to 3 carbonyl groups, sulfinyl groups or sulfonyl groups in the ring; and
    5. (5) being monocyclic or bicyclic. In the case of containing a nitrogen atom as a ring member, the nitrogen atom may have a binding hand. Specific examples include an aziridinyl group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, an azepanyl group, an azocanyl group, a piperazinyl group, a diazepanyl group, a diazocanyl group, a diazabicyclo[2.2.1]heptyl group, a morpholinyl group, a thiomorpholinyl group, a 1,1-dioxothiomorpholinyl group, an oxilanyl group, an oxetanyl group, a tetrahydrofuryl group, a dioxolanyl group, a tetrahydropyranyl group, a dioxanyl group, a tetrahydrothienyl group, a tetrahydrothiopyranyl group, an oxazolidinyl group, and a thiazolidinyl group.
  • Preferred examples of the "3- to 10-membered non-aromatic heterocyclic group" may include an aziridinyl group, an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, an azepanyl group, a piperazinyl group, a diazepanyl group, a morpholinyl group, a thiomorpholinyl group, a 1,1-dioxothiomorpholinyl group, a tetrahydrofuryl group, and a tetrahydropyranyl group.
  • As used herein, the term "C1-6 alkoxy group" refers to a group having an oxygen atom attached to the end of the "C1-6 alkyl group" defined above. Specific examples include a methoxy group, an ethoxy group, a 1-propoxy group (i.e., a n-propoxy group), a 2-propoxy group (i.e., an i-propoxy group), a 2-methyl-1-propoxy group (i.e., an i-butoxy group), a 2-methyl-2-propoxy group (i.e., a t-butoxy group), a 1-butoxy group (i.e., a n-butoxy group), a 2-butoxy group (i.e., a s-butoxy group), a 1-pentyloxy group, a 2-pentyloxy group, a 3-pentyloxy group, a 2-methyl-1-butoxy group, a 3-methyl-1-butoxy group, a 2-methyl-2-butoxy group, a 3-methyl-2-butoxy group, a 2,2-dimethyl-1-propoxy group, a 1-hexyloxy group, a 2-hexyloxy group, a 3-hexyloxy group, a 2-methyl-1-pentyloxy group, a 3-methyl-1-pentyloxy group, a 4-methyl-1-pentyloxy group, a 2-methyl-2-pentyloxy group, a 3-methyl-2-pentyloxy group, a 4-methyl-2-pentyloxy group, a 2-methyl-3-pentyloxy group, a 3-methyl-3-pentyloxy group, a 2,3-dimethyl-1-butoxy group, a 3,3-dimethyl-1-butoxy group, a 2,2-dimethyl-l-butoxy group, a 2-ethyl-1-butoxy group, a 3,3-dimethyl-2-butoxy group, and a 2,3-dimethyl-2-butoxy group.
  • Preferred examples of the "C1-6 alkoxy group" may include "C1-4 alkoxy groups," as exemplified by a methoxy group, an ethoxy group, a 1-propoxy group, a 2-propoxy group, a 2-methyl-1-propoxy group, a 2-methyl-2-propoxy group, a 1-butoxy group, and a 2-butoxy group.
  • As used herein, the term "C1-6 alkylthio group" refers to a group having a sulfur atom attached to the end of the "C1-6 alkyl group" defined above. Specific examples include a methylthio group, an ethylthio group, a 1-propylthio group (i.e., a n-propylthio group), a 2-propylthio group (i.e., an i-propylthio group or an isopropylthio group), a 2-methyl-1-propylthio group (i.e., an i-butylthio group or an isobutylthio group), a 2-methyl-2-propylthio group (i.e., a t(tert)-butylthio group), a 1-butylthio group (i.e., a n-butylthio group), a 2-butylthio group (i.e., a s(sec)-butylthio group), a 1-pentylthio group, a 2-pentylthio group, a 3-pentylthio group, a 2-methyl-1-butylthio group, a 3-methyl-1-butylthio group, a 2-methyl-2-butylthio group, a 3-methyl-2-butylthio group, a 2,2-dimethyl-1-propylthio group, a 1-hexylthio group, a 2-hexylthio group, a 3-hexylthio group, a 2-methyl-1-pentylthio group, a 3-methyl-1-pentylthio group, a 4-methyl-1-pentylthio group, a 2-methyl-2-pentylthio group, a 3-methyl-2-pentylthio group, a 4-methyl-2-pentylthio group, a 2-methyl-3-pentylthio group, a 3-methyl-3-pentylthio group, a 2,3-dimethyl-1-butylthio group, a 3,3-dimethyl-1-butylthio group, a 2,2-dimethyl-1-butylthio group, a 2-ethyl-1-butylthio group, a 3,3-dimethyl-2-butylthio group, and a 2,3-dimethyl-2-butylthio group.
  • Preferred examples of the "C1-6 alkylthio group" may include "C1-4 alkylthio groups," as exemplified by a methylthio group, an ethylthio group, a 1-propylthio group, a 2-propylthio group, a 2-methyl-1-propylthio group, a 2-methyl-2-propylthio group, a 1-butylthio group, and a 2-butylthio group.
  • As used herein, the term "C3-8 cycloalkoxy group" refers to a group having an oxygen atom attached to the end of the "C3-8 cycloalkyl group" defined above. Specific examples include a cyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a cyclohexyloxy group, a cycloheptyloxy group, a cyclooctyloxy group, a bicyclo[2.1.0]pentyloxy group, a bicyclo[3.1.0]hexyloxy group, a bicyclo[2.1.1]hexyloxy group, a bicyclo[4.1.0]heptyloxy group, a bicyclo[2.2.1]heptyloxy group (i.e., a norbornyloxy group), a bicyclo[3.3.0]octyloxy group, a bicyclo[3.2.1]octyloxy group, and a bicyclo[2.2.2]octyloxy group.
  • Preferred examples of the "C3-8 cycloalkoxy group" may include a cyclopropoxy group, a cyclobutoxy group, and a cyclopentyloxy group.
  • As used herein, the term "mono-C1-6 alkylamino group" refers to an amino group whose one hydrogen atom is replaced by the "C1-6 alkyl group" defined above. Specific examples include a methylamino group, an ethyl amino group, a 1-propylamino group (i.e., a n-propylamino group), a 2-propylamino group (i.e., an i-propylamino group), a 2-methyl-1-propylamino group (i.e., an i-butylamino group), a 2-methyl-2-propylamino group (i.e., a t-butylamino group), a 1-butylamino group (i.e., a n-butylamino group), a 2-butylamino group (i.e., a s-butylamino group), a 1-pentylamino group, a 2-pentylamino group, a 3-pentylamino group, a 2-methyl-1-butylamino group, a 3-methyl-1-butylamino group, a 2-methyl-2-butylamino group, a 3-methyl-2-butylamino group, a 2,2-dimethyl-1-propylamino group, a 1-hexylamino group, a 2-hexylamino group, a 3-hexylamino group, a 2-methyl-1-pentylamino group, a 3-methyl-1-pentylamino group, a 4-methyl-1-pentylamino group, a 2-methyl-2-pentylamino group, a 3-methyl-2-pentylamino group, a 4-methyl-2-pentylamino group, a 2-methyl-3-pentylamino group, a 3-methyl-3-pentylamino group, a 2,3-dimethyl-1-butylamino group, a 3,3-dimethyl-1-butylamino group, a 2,2-dimethyl-1-butylamino group, a 2-ethyl-1-butylamino group, a 3,3-dimethyl-2-butylamino group, and a 2,3-dimethyl-2-butylamino group.
  • As used herein, the term "di-C1-6 alkylamino group" refers to an amino group whose two hydrogen atoms are replaced by the same or different "C1-6 alkyl groups" defined above. Specific examples include an N,N-dimethylamino group, an N,N-diethylamino group, an N,N-di-n-propylamino group, an N,N-di-i-propylamino group, an N,N-di-n-butylamino group, an N,N-di-i-butylamino group, an N,N-di-s-butylamino group, an N,N-di-t-butylamino group, an N-ethyl-N-methylamino group, an N-n-propyl-N-methylamino group, an N-i-propyl-N-methylamino group, an N-n-butyl-N-methylamino group, an N-i-butyl-N-methylamino group, an N-s-butyl-N-methylamino group, and an N-t-butyl-N-methylamino group.
  • As used herein, the term "C2-7 acyl group" refers to a carbonyl group, to which the "C1-6 alkyl group" defined above is attached. Specific examples include, for example, an acetyl group, a propionyl group, an isopropionyl group, a butyryl group, an isobutyryl group, a valeryl group, an isovaleryl group, and a pivaloyl group.
  • As used herein, the term "C2-7 alkoxycarbonyl group" refers to a carbonyl group, to which the "C1-6 alkoxy group" defined above is attached. Specific examples include, for example, a methoxycarbonyl group, an ethoxycarbonyl group, a 1-propyloxycarbonyl group, a 2-propyloxycarbonyl group, and a 2-methyl-2-propoxy group (i.e., a t-butoxycarbonyl group).
  • As used herein, the term "C2-5 alkoxycarbonyl group" refers to a carbonyl group, to which the "C1-4 alkoxy group" defined above is attached. Specific examples include, for example, a methoxycarbonyl group, an ethoxycarbonyl group, a 1-propyloxycarbonyl group, a 2-propyloxycarbonyl group, and a 2-methyl-2-propoxy group.
  • As used herein, the phrase "optionally substituted" or "substituted" means "optionally having one or more substituents in any combination at a substitutable site(s)" or "having one or more substituents in any combination at a substitutable site(s)." As used herein, specific examples of substituents include, for example, a halogen atom, a hydroxyl group, a thiol group, a nitro group, a cyano group, a formyl group, a carboxyl group, an amino group, a silyl group, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 5- to 10-membered heteroaryl group, a 3- to 10-membered non-aromatic heterocyclic group, a C1-6 alkoxy group, a C1-6 alkylthio group, a C3-8 cycloalkoxy group, a mono-C1-6 alkylamino group, a di-C1-6 alkylamino group, a C2-7 acyl group or a C2-7 alkoxycarbonyl group (provided that the amino group, the C1-6 alkyl group, the C2-6 alkenyl group, the C2-6 alkynyl group, the C3-8 cycloalkyl group, the C6-10 aryl group, the 5- to 10-membered heteroaryl group, the 3- to 10-membered non-aromatic heterocyclic group, the C1-6 alkoxy group, the C1-6 alkylthio group, the C3-8 cycloalkoxy group, the mono-C1-6 alkylamino group, the di-C1-6 alkylamino group, the C2-7 acyl group and the C2-7 alkoxycarbonyl group may each independently have 1 to 3 groups selected from the group consisting of the following substituent group). In the present invention, substituents other than those listed above may be intended in some cases.
    • <Substituent group>
  • A halogen atom, a hydroxyl group, a thiol group, a nitro group, a cyano group, a silyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C6-10 aryl group, a 5- to 10-membered heteroaryl group, a 3- to 10-membered non-aromatic heterocyclic group, a C1-6 alkoxy group and a C1-6 alkylthio group.
    • 1. Sulfonamide-including compounds
  • In the present invention, the sulfonamide-including compound includes compounds of the following Formula (I):
    Figure imgb0008
  • In the above Formula (I), E represents -O-, -N(CH3)-, -CH2-, -CH2CH2- or -CH2O-, D represents -CH2- or -O-, R1a represents a hydrogen atom or a halogen atom, and R2a represents a halogen atom or a trifluoromethyl group.
  • The compounds of Formula (I) according to the present invention can be prepared in a known manner, for example as described in European Patent Publication No. 0222475A1 .
  • In Formula (I), a preferred compound is LY186641 or LY295501.
  • LY186641 refers to N-[[(4-chlorophenyl)amino]carbonyl]-2,3-dihydro-1H-indene-5-sulfonamide and its structural formula is shown in the following Formula (VII):
    Figure imgb0009
  • LY186641 can be prepared in a known manner, for example as described in European Patent Publication No. 0222475A1 .
  • In the present invention, LY295501 refers to N-[[(3,4-dichlorophenyl)amino]-carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide and its structural formula is shown in the following Formula (VIII):
    Figure imgb0010
  • LY295501 can be prepared in a known manner, for example as described in European Patent Publication No. 0222475A1 and/or European Patent Publication No. 0555036A2 .
  • In the present invention, the sulfonamide-including compound also includes compounds of the following Formula (II):
    Figure imgb0011
  • In Formula (II), J represents -O- or -NH-, R1b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted C1-4 alkylthio group, an optionally substituted C2-5 alkoxycarbonyl group, a nitro group, an azido group, -O(SO2)CH3, -N(CH3)2, a hydroxyl group, a phenyl group, a substituted phenyl group, a pyridinyl group, a thienyl group, a furyl group, a quinolinyl group or a triazole group, R2b represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-5 alkoxycarbonyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted phenyl group or an optionally substituted quinolinyl group, R3b represents a hydrogen atom or an optionally substituted C1-4 alkoxy group, R4b represents a hydrogen atom or an optionally substituted C1-6 alkyl group (provided that at least one of R3b and R4b is a hydrogen atom), R5b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group or a nitro group, R6b represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group (provided that when R6b is an optionally substituted C1-6 alkyl group, R5b is a hydrogen atom and R7b is a halogen atom), and R7b represents a halogen atom or an optionally substituted C1-6 alkyl group (provided that when either R5b or R7b is an optionally substituted C1-6 alkyl group or when R7b is a halogen atom or an optionally substituted C1-6 alkyl group, either R5b or R6b is a hydrogen atom).
  • In Formula (II), the "C1-6 alkyl group" may preferably include a methyl group, an ethyl group, a 1-propyl group, a 2-propyl group, a 2-methyl-1-propyl group, a 2-methyl-2-propyl group, a 1-butyl group, and a 2-butyl group. Among them, most preferred are a methyl group, an ethyl group, a 1-propyl group, and a 2-propyl group.
  • Likewise, in Formula (II), the optionally substituted C1-6 alkyl group may be, for example, a trifluoromethyl group.
  • In Formula (II), the "C1-4 alkoxy group" may preferably include a methoxy group, an ethoxy group, a 1-propoxy group, a 2-propoxy group, and a 1-butoxy group.
  • Likewise, in Formula (II), the optionally substituted C1-4 alkoxy group may be, for example, -OCF3.
  • In Formula (II), the "C1-4 alkylthio group" may preferably include a methylthio group, an ethylthio group, a 1-propylthio group, a 2-propylthio group, a 2-methyl-1-propylthio group, a 2-methyl-2-propyl group, a 1-butylthio group, and a 2-butylthio group.
  • Likewise, in Formula (II), the optionally substituted C1-4 alkylthio group may be, for example, -SCF3.
  • In Formula (II), the "C2-5 alkoxycarbonyl group" may preferably include a methoxycarbonyl group, an ethoxycarbonyl group, a 1-propyloxycarbonyl group, a 2-propyloxycarbonyl group, and a t-butoxycarbonyl group.
  • In Formula (II), examples of substituents to be introduced may include those exemplified by a C1-6 alkyl group, a C1-4 alkoxy group, an amino group, a hydroxyl group, a halogen atom or a silyl group.
  • The compounds of Formula (II) according to the present invention can be prepared in a known manner, for example as described in International Publication No. WO02/098848 .
  • In Formula (II), a preferred compound is LY-ASAP.
  • LY-ASAP refers to N-(2,4-dichlorobenzoyl)-4-chlorophenylsulfonamide and its structural formula is shown in the following Formula (XI):
    Figure imgb0012
  • LY-ASAP can be prepared in a known manner, for example as described in International Publication No. WO02/098848 .
  • In the present invention, the sulfonamide-including compound may also include LY573636. In the present invention, LY573636 refers to N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide and its structural formula is shown in the following Formula (III):
    Figure imgb0013
  • LY573636 is preferably in sodium salt form.
  • LY573636 can be prepared in a known manner, for example, in the same manner as described in International Publication No. WO02/098848 , starting with commercially available 5-bromothiophene-2-sulfonyl chloride and 2,4-dichlorobenzoic acid.
  • In the present invention, the sulfonamide-including compound may also include CQS. In the present invention, CQS refers to 2-sulfanylamido-5-chloroquinoxaline and its structural formula is shown in the following Formula (IV):
    Figure imgb0014
  • CQS can be prepared in a known manner, for example as described in J. Am. Chem. Soc., 1947, 71, 6-10.
  • Moreover, in the present invention, the sulfonamide-including compound may also include E7070. E7070 refers to N-(3-chloro-1H-indol-7-yl)4-sulfamoylbenzenesulfonamide and its structural formula is shown in the following Formula (IX):
    Figure imgb0015
  • E7070 can be prepared in a known manner, for example as described in International Publication No. WO95/07276 or in Example 19 of JP 7-165708 A .
  • In the present invention, the sulfonamide-including compound also includes compounds of the following Formula (XIV).
    Figure imgb0016
  • In the above Formula (XIV),
    • the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    • the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    • the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    • W represents a single bond or -CH=CH-,
    • X represents -N(R1)- or an oxygen atom,
    • Y represents:
      Figure imgb0017
       and
    • Z represents -N(R2)-.
  • In these formulae, R1, R2 and R3, which may be the same or different, each independently represents a hydrogen atom or a lower alkyl group.
  • The "optionally substituted monocyclic or bicyclic aromatic ring" defined for the ring A refers to an aromatic hydrocarbon or an aromatic heterocyclic ring containing at least one of a nitrogen atom, an oxygen atom and a sulfur atom. Such a ring may have 1 to 3 substituents. Examples of major aromatic rings encompassed by the ring A may include pyrrole, pyrazole, imidazole, thiophene, furan, thiazole, oxazole, benzene, pyridine, pyrimidine, pyrazine, pyridazine, naphthalene, quinoline, isoquinoline, phthalazine, naphthylizine, quinoxaline, quinazoline, cinnoline, indole, isoindole, indolizine, indazole, benzofuran, benzothiophene, benzoxazole, benzimidazole, benzopyrazole, and benzothiazole. These aromatic rings may have 1 to 3 substituents, which may be the same or different. Examples of substituents may include an optionally lower alkyl- or lower cycloalkyl-substituted amino group, a lower alkyl group, a lower alkoxy group, a hydroxyl group, a nitro group, a mercapto group, a cyano group, a lower alkylthio group, a halogen atom, a group represented by the formula -a-b [wherein a represents a single bond, -(CH2)k-, -O-(CH2)k-, -S-(CH2)k- or -N(R3)-(CH2)k-, k represents an integer of 1 to 5, R3 represents a hydrogen atom or a lower alkyl group, and b represents -CH2- d (wherein d represents an optionally lower alkyl-substituted amino group, a halogen atom, a hydroxyl group, a lower alkylthio group, a cyano group or a lower alkoxy group)], a group represented by the formula -a-e-f [wherein a is as defined above, e represents -S(O)- or -S(O)2-, and f represents an optionally lower alkyl- or lower alkoxy-substituted amino group, a lower alkyl group, a trifluoromethyl group, -(CH2)m-b or -N(R4)-(CH2)m-b (wherein b is as defined above, R4 represents a hydrogen atom or a lower alkyl group, and m represents an integer of 1 to 5)], a group represented by the formula -a-g-h [wherein a is as defined above, g represents - C(O)- or -C(S)-, and h represents an optionally lower alkyl-substituted amino group, a hydroxyl group, a lower alkyl group, a lower alkoxy group, -(CH2)n-b or -N(R5)-(CH2)n-b (wherein b is as defined above, R5 represents a hydrogen atom or a lower alkyl group, and n represents an integer of 1 to 5)], a group represented by the formula -a-N(R6)-g-i [wherein a and g are as defined above, R6 represents a hydrogen atom or a lower alkyl group, and i represents a hydrogen atom, a lower alkoxy group or f (wherein f is as defined above)], a group represented by the formula -a-N(R7)-e-f (wherein a, e and f are as defined above, and R7 represents a hydrogen atom or a lower alkyl group), or a group represented by the formula - (CH2)p-j-(CH2)q-b (wherein j represents an oxygen atom or a sulfur atom, b is as defined above, and p and q, which may be the same or different, each represent an integer of 1 to 5).
  • In the above examples of substituents, in the case of an amino group substituted with two alkyl groups, these alkyl groups may together form a 5- or 6-membered ring. Likewise, in a case where the ring A is a nitrogen-containing heterocyclic ring having a hydroxyl group or a mercapto group, these groups may form an oxo group or a thioxo group by taking the resonance structure.
  • In Formula (XIV), the "optionally substituted 6-membered cyclic unsaturated hydrocarbon" or the "optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom" defined for the ring B refers to, for example, benzene or pyridine whose unsaturated bonds may be partially hydrogenated. Such a ring may have one or more substituents, which may be the same or different.
  • The "optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms" defined for the ring C refers to pyrrole, pyrazole or imidazole whose unsaturated bonds may be partially hydrogenated. Such a ring may have one or two substituents, which may be the same or different.
  • In Formula (XIV), Z represents -N(R2)-. R2 may be the same as or different from R1 described later and represents a hydrogen atom or a lower alkyl group.
  • Examples of substituents which may be on the rings B and C include a halogen atom, a cyano group, a lower alkyl group, a lower alkoxy group, a hydroxyl group, an oxo group, a group represented by the formula -C(O)-r (wherein r represents a hydrogen atom, an optionally lower alkyl-substituted amino group, a lower alkyl group, a lower alkoxy group or a hydroxyl group), an optionally lower alkyl-substituted amino group, and a trifluoromethyl group.
  • In Formula (XIV), Y represents:
    Figure imgb0018
     In the above formula, R3 represents a hydrogen atom or a lower alkyl group.
  • In Formula (XIV), W represents a single bond or -CH=CH-, and X represents -N(R1)- or an oxygen atom. R1 may be the same as or different from R2 and represents a hydrogen atom or a lower alkyl group.
  • In the above Formula (XIV), the "lower alkyl (group)" found in the definition of substituents which may be on R1, R2 and R3 as well as the rings A, B and C refers to a linear or branched alkyl group containing 1 to 6 carbon atoms and has the same meaning as the "C1-6 alkyl group" mentioned above.
  • The "lower cycloalkyl (group)" found in the definition of substituents which may be on the ring A refers to a cycloalkyl group containing 3 to 8 carbon atoms and has the same meaning as the "C3-8 cycloalkyl group" mentioned above. Examples of such a lower cycloalkyl group include a cyclopropyl group, a cyclopentyl group, and a cyclohexyl group. Likewise, the "lower alkylthio (group)" refers to an alkylthio group derived from the above lower alkyl group and has the same meaning as the "C1-6 alkylthio group" mentioned above.
  • The "lower alkoxy (group)" found in the definition of substituents which may be on the rings A, B and C refers to, for example, a lower alkoxy group derived from the above lower alkyl group, as exemplified by a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, a n-butoxy group, an isobutoxy group, and a tert-butoxy group. Among them, most preferred are a methoxy group and an ethoxy group. Likewise, examples of the "halogen atom" include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • The compounds of Formula (XIV) according to the present invention can be prepared in a known manner, for example as described in International Publication No. WO95/07276 and/or JP 7-165708 A .
  • In Formula (I), a preferred compound is the E7070 mentioned above or E7820.
  • E7820 refers to N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide and its structural formula is shown in the following Formula (X):
    Figure imgb0019
  • E7820 can be prepared in a known manner, for example as described in International Publication No. WO00/50395 .
  • These sulfonamide-including compounds may form pharmacologically acceptable salts with acids or bases. The compounds according to the present invention also encompass these pharmacologically acceptable salts. Examples of salts with acids include inorganic acid salts (e.g., hydrochloride salt, hydrobromide salt, sulfate salt, phosphate salt), as well as salts with organic acids such as formic acid, acetic acid, lactic acid, succinic acid, fumaric acid, maleic acid, citric acid, tartaric acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and trifluoroacetic acid. Likewise, examples of salts with bases include alkali metal salts (e.g., sodium salt, potassium salt), alkaline earth metal salts (e.g., calcium salt, magnesium salt), salts with organic bases such as trimethylamine, triethylamine, pyridine, picoline, dicyclohexylamine, N,N'-dibenzylethylenediamine, arginine and lysine (organic amine salts), as well as ammonium salts.
  • Alternatively, these sulfonamide-including compounds may be in anhydride form or may form solvates such as hydrates. Solvates may be either hydrates or anhydrates, preferably hydrates. Solvents available for use include water, alcohols (e.g., methanol, ethanol, n-propanol) and dimethylformamide..
  • In a case where these compounds are present in solvate form and/or have optical isomers, the compounds according to the present invention also encompass their solvates and/or optical isomers. The compounds according to the present invention further encompass sulfonamide-including compounds that are metabolized in vivo by oxidation, reduction, hydrolysis, conjugation, etc. Furthermore, the compounds according to the present invention encompass compounds that produce sulfonamide-including compounds when metabolized in vivo by oxidation, reduction, hydrolysis, etc.
    • 2. Angiogenesis inhibitors
  • As a result of combining a sulfonamide-including compound with an angiogenesis inhibitor, the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity.
  • For convenience purposes, the angiogenesis inhibitor is also referred to as an angiogenesis inhibitory agent in the following explanation.
  • In the present invention, the angiogenesis inhibitor is not limited in any way as long as it has an inhibitory activity on angiogenesis. Examples of such an angiogenesis inhibitor include VEGF (vascular endothelial growth factor) inhibitors (e.g., VEGF receptor kinase inhibitors, anti-VEGF antibodies (Cancer Research., 55, 5296-5301, 1995)), FGF (fibroblast growth factor) inhibitors (e.g., FGF receptor kinase inhibitors, anti-FGF antibodies (Cancer Research., 51, 6180-4, 1991)), PDGF (platelet-derived growth factor) inhibitors (e.g., PDGF receptor kinase inhibitors (J. Clinical Investigation., 111, 1287-95)), integrin inhibitors (e.g., αvβ3 integrin inhibitors, αvβ5 integrin inhibitors (Clinical Cancer Research., 6, 3056-61, 2000)), endogenous inhibitors (e.g., IL-12, Trombospondin-1, Endostatin, Angiostatin (International J. Cancer., 78, 361-5, 1998), COX-2 inhibitors (Annuals of N.Y Acad. Science., 84-6, 1999)), matrix metalloprotein inhibitors (International J. Pancreatol., 21, 1-12, 1997), as well as other inhibitors (e.g., farnesyltransferase inhibitors, nitric oxide inhibitors, angiotensin converting enzyme inhibitors, HMG-CoA reductase inhibitors, Vascular Target inhibitors, methionine aminopeptidase inhibitors (Science., 282, 1324-1327, 1998)). Preferred examples are VEGF receptor kinase inhibitors, anti-VEGF antibodies, FGF receptor kinase inhibitors and anti-FGF antibodies, and more preferred examples are VEGF receptor kinase inhibitors and anti-VEGF antibodies.
    • (1) VEGF receptor kinase inhibitors
  • In the present invention, the VEGF receptor kinase inhibitor may include, for example, compounds of Formula (XXIV):
    Figure imgb0020
    1. (i) Ad
      • Ad represents a group represented by the following formula:
        Figure imgb0021
         (wherein R1d' represents a group represented by the formula -V1-V2-V3 (wherein V1 represents an optionally substituted C1-6 alkylene group; V2 represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6d-, a group represented by the formula-SO2NR6d-, a group represented by the formula -NR6dSO2-, a group represented by the formula -NR6dCO- or a group represented by the formula -NR6d- (wherein R6d represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
      • R2d' represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVa11Va12 (wherein Va11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Va12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
      • A1 represents an optionally substituted carbon atom or a nitrogen atom;
      • R11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
      • R12 represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
      • Va13 represents an oxygen atom or a sulfur atom;
      • A11 represents an optionally substituted carbon atom or a nitrogen atom;
      • R13 represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group; and
      • R14 represents a group represented by the formula -Va14-Va15 (wherein Va14 represents a single bond or a carbonyl group; and Va15 represents a hydrogen atom, a hydroxyl group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, an amino group, an optionally substituted mono-C1-6 alkylamino group, an optionally substituted di-C1-6 alkylamino group, a formyl group, a carboxyl group or an optionally substituted C2-7 alkoxycarbonyl group)).
    2. (ii) Xd
      • Xd represents an oxygen atom or a sulfur atom.
    3. (iii) Yd
      • Yd represents a group represented by the following formula:
        Figure imgb0022
         (wherein R3d' represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
      • R7d and R8d each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C1-6 alkylthio group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula - CONVd1Vd2 (wherein Vd1 and Vd2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group);
      • R9d represents a hydrogen atom, a halogen atom or a C1-6 alkyl group; and
      • W1 and W2 each independently represent an optionally substituted carbon atom or a nitrogen atom).
    4. (iv) R4d
      • R4d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group.
    5. (v) R5d
      • R5d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group.
  • The compounds of Formula (XXIV) can be prepared in a known manner, for example as described in International Publication No. WO02/032872 , International Publication No. WO2004/020434 , and/or International Publication No. WO2005/063713 .
  • In the present invention, the VEGF receptor kinase inhibitor may preferably include compounds of Formula (XXV):
    Figure imgb0023
     Formula (XXV) is a preferred example of the compounds of Formula (XXIV).
    • (i) R1e
  • R1e represents a group represented by the formula -V1e-V2e-V3e (wherein V1e represents an optionally substituted C1-6 alkylene group; V2e represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6e-, a group represented by the formula -SO2NR6e-, a group represented by the formula -NR6eSO2-, a group represented by the formula -NR6eCO- or a group represented by the formula -NR6e- (wherein R6e represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group).
  • Preferred examples of R1e include a C1-6 alkyl group. In this case, however, R1e may have one or more substituents selected from a 3- to 10-membered non-aromatic heterocyclic group which may have a C1-6 alkyl group, a hydroxyl group, a C1-6 alkoxy group, an amino group, a mono-C1-6 alkylamino group and a di-C1-6 alkylamino group.
  • More preferred examples of R1e include a methyl group or a group represented by any of the following formulae:
    Figure imgb0024
     (wherein Ra3 represents a methyl group; Ra1 represents a hydrogen atom or a hydroxyl group; and Ra2 represents a methoxy group, an ethoxy group, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group).
  • Even more preferred examples of R1e include a methyl group or a 2-methoxyethyl group.
    • (ii) R2e
  • R2e represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group).
  • Preferred examples of R2e include a cyano group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 and Ve12 are as defined above).
  • More preferred examples of R2e include a cyano group or a group represented by the formula -CONHVe16 (wherein Ve16 represents a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group or a C3-8 cycloalkoxy group, provided that Ve16 may have one or more substituents selected from a halogen atom, a cyano group, a hydroxyl group and a C1-6 alkoxy group).
  • Even more preferred examples of R2e include a group represented by the formula - CONHVe17 (wherein Ve17 represents a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group).
  • Most preferred examples of R2e include a group represented by the formula - CONHVe18 (wherein Ve18 represents a hydrogen atom, a methyl group or a methoxy group).
    • (iii) Y1
  • Y1represents a group represented by the following formula:
    Figure imgb0025
     (wherein R7e and R8e each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe1Ve2 (wherein Ve1 and Ve2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group); and
  • W1e and W2e each independently represent an optionally substituted carbon atom or a nitrogen atom).
  • Preferred examples of Y1 include a group represented by the following formula:
    Figure imgb0026
     (wherein R71 represents a hydrogen atom or a halogen atom).
    • (iv) R3e and R4e
  • R3e and R4e each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group.
  • Preferred examples of R3e and R4e include a hydrogen atom.
    • (v) R5e
  • R5e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group.
  • Preferred examples of R5e include a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group or a C6-10 aryl group (provided that R5e may have one or more substituents selected from a halogen atom and a methanesulfonyl group).
  • More preferred examples of R5e include a methyl group, an ethyl group or a cyclopropyl group.
  • Moreover, preferred examples of the compounds of Formula (XXV) may include compounds of Formula (V):
    Figure imgb0027
     [wherein R1c represents a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or a cyclopropyl group, and R2c represents -NH2 or -NHOCH3].
  • R1c may have a substituent such as an alkyl group (e.g., a methyl group, an ethyl group, a propyl group, a butyl group), an alkoxy group (e.g., a methoxy group, an ethoxy group, a propoxy group, a butoxy group), an amino group, a hydroxyl group, a halogen atom or a silyl group.
  • Preferred examples of the compounds of Formula (XXV) may also include:
    • N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-(4-fluorophenyl)urea,
    • N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    • N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    • N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    • 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    • N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide,
    • 4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    • N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    • N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoary)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • N6-methyl-4-(3-chloro-4-(((cydopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    • N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    • N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    • N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    • N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    • N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    • N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    • N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    • N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    • N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N'-(3-(methylsulfonyl)phenyl)urea,
    • 4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic acid (2-cyanoethyl)amide, and
    • N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea.
  • More preferred examples of the compounds of Formula (XXV) may include:
    • 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    • N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    • 4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, and
    • N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide.
  • Even more preferred examples of the compounds of Formula (XXV) may include 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide (see Formula (XV)), and the most preferred example may be a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
    Figure imgb0028
  • The compounds of Formula (XXV) can be prepared in a known manner, for example as described in International Publication No. WO02/03287 and/or International Publication No. WO2005/063713 .
  • In the present invention, the VEGF receptor kinase inhibitor may also preferably include compounds of Formula (XXVI):
    Figure imgb0029
     Formula (XXVI) is a preferred example of the compounds of Formula (XXIV).
    • (i) R11f
  • R11f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group.
  • Preferred examples of R11f include an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group.
  • More preferred examples of R11f include any one group selected from those represented by the following formulae:
    Figure imgb0030
    Figure imgb0031
     which may have one or more substituents selected from the following substituent group:
    • [Substituent group]
  • a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0032
    Figure imgb0033
     (wherein RN1 and RN2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group; and Me denotes a methyl group).
  • Even more preferred examples of R11f include any one group selected from those represented by the following formulae:
    Figure imgb0034
    • (ii) R12f
  • R12f represents a hydrogen atom or an optionally substituted C1-6 alkyl group.
  • Preferred examples of R12f include a hydrogen atom.
    • (iii) Vf13
  • Vf13 represents an oxygen atom or a sulfur atom.
  • Preferred examples of Vf13 include an oxygen atom.
    • (iv) A11f
  • A11f represents an optionally substituted carbon atom or a nitrogen atom.
  • Preferred examples of A11f include a carbon atom.
    • (v) R4f
  • R4f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group.
  • Preferred examples of R4f include a hydrogen atom.
    • (vi) R5f
  • R5f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group.
  • Preferred examples of R5f include a C1-6 alkyl group or a C3-8 cycloalkyl group.
  • More preferred examples of R5f include a methyl group.
    • (vii) R9f
  • R9f represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group.
  • Preferred examples of R9f include a hydrogen atom.
  • Moreover, preferred examples of the compounds of Formula (XXVI) may include compounds of Formula (VI):
    Figure imgb0035
  • In Formula (VI), R1d represents any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0036
    Figure imgb0037
     which may have one or more substituents selected from the substituent group α, and R2d represents -NHR3d (wherein R3d represents a methyl group, an ethyl group or a cyclopropyl group), provided that the substituent group α denotes a group consisting of a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0038
    Figure imgb0039
     (wherein RN1' and RN2' each independently represent a hydrogen atom or a C1-6 alkyl group).
  • R3d may have a substituent such as an alkyl group (e.g., a methyl group, an ethyl group, a propyl group, a butyl group), an alkoxy group (e.g., a methoxy group, an ethoxy group, a propoxy group, a butoxy group), an amino group, a hydroxyl group, a halogen atom (e.g., fluorine, chlorine, bromine, iodine) or a silyl group. Examples of substituents introduced into RN1' or RN2' may include the same substituents as mentioned above.
  • Preferred examples of the compounds of Formula (XXVI) may also include:
    • 5-(2-(((4-hydroxy-4-methylpiperidiri-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide,
    • N1-methyl-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide,
    • N1-methyl-5-(2-(((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide,
    • N1-methyl-5-(2-(((4-(piperidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide, and
    • N4-(4-(1-(methylamino)carbonyl-1H-5-indolyl)oxy-2-pyridyl)-4-morpholinecarboxamide.
  • The compounds of Formula (XXVI) can be prepared in a known manner, for example as described in International Publication No. W02004/020434 .
  • In the present invention, the VEGF receptor kinase inhibitor may include, for example:
    1. (1) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]quinazoline-4-amine (hereinafter also referred to as "ZD4190"; Cancer Research., 60, 970-975, 2000, Journal of Medicinal Chemistry., 42: 5369-5389, 1999),
    2. (2) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline-4-amine (hereinafter also referred to as "ZD6474"; Proc. Am. Assoc. Cancer Res., 42,583,2001, Journal of Medicinal Chemistry., 45: 1300-1312,2002),
    3. (3) 3-[(2,4-dimethylpyrrol-5-yl)methylene]-2-indolinone (hereinafter also referred to as "SU5416"; Cancer Res., 59, 99-106, 1999, Journal of Medicinal Chemistry, 41: 2588-2603, 1998, US5792783 ),
    4. (4) (Z)-3-(2,4-dimethyl-5-(2-oxo-1,2-dihydroindol-3-ylidenemethyl)-1H-pyrrol-3-yl)-propionic acid (hereinafter also referred to as "SU6668"; Cancer Res., 60, 4152-4160, 2000, Journal of Medicinal Chemistry., 42: 5120-5130, 1999),
    5. (5) 5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide (hereinafter also referred to as "SU11248"; Clinical Cancer Research, 9, 327-337, 2003, Journal of Medicinal Chemistry., 46: 1116-9, 2003),
    6. (6) N,N-dimethylglycine 3-{5,6,7,13-tetrahydro-9-[(1-methylethoxy)methyl]-5-oxo-12H-indeno(2,1-a)pyrrolo(3,4-c)carbazol-12-yl}propyl ester (hereinafter also referred to as "CEP-7055"; Pro. Am. Assoc. Cancer Research, 43, 1080, 2002, Journal of Medicinal Chemistry., 46: 5375-88, 2003),
    7. (7) 3-(4-bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide (hereinafter also referred to as "CP-547,632"; Proc. Am. Soc. Clin. Oncology, 21, (Abstract 16), 2002, Cancer Research. 63:7301-9, 2003, WO 99/62890 ),
    8. (8) N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea (hereinafter also referred to as "KRN633"; Pro. Am. Assoc. Cancer Research, 43, 175, 2002, Molecular Cancer Therapeutics., 3:1639-49, 2004),
    9. (9) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine (hereinafter also referred to as "PTK787"; Cancer Research, 60, 2179-2189, 2000, Journal of Medicinal Chemistry., 43:2310-23, 2000, WO98/35958 ) (see Formula (XII) for (1) to (9)),
    10. (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea (hereinafter also referred to as "KRN951"; Proceedings of the American Association for Cancer Research, 45, 594, (Abstract 2571), 2004, Proceedings of the American Association for Cancer Research, 45, 595, (Abstract 2575), 2004),
    11. (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1- yl)propoxy]quinazoline (hereinafter also referred to as "AZD2171"; Cancer Research. 65:4389-400, 2005, WO00/47212 ), and
    12. (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole (hereinafter also referred to as "AG013736"; American Journal of Pathology. 165:35-52, 2004) (see Formula (XIII) for (10) to (12)).
  • ZD4190 (Cancer Research., 60, 970-975, 2000, Journal of Medicinal Chemistry., 42: 5369-5389, 1999), ZD6474 (Proc. Am. Assoc. Cancer Res., 42, 583, 2001, Journal of Medicinal Chemistry., 45: 1300-1312, 2002), SU5416 (Cancer Res., 59, 99-106, 1999, Journal of Medicinal Chemistry., 41: 2588-2603, 1998), SU6668 (Cancer Res., 60, 4152-4160, 2000, Journal of Medicinal Chemistry., 42: 5120-5130, 1999), SU11248 (Clinical Cancer Research, 9, 327-337, 2003, Journal of Medicinal Chemistry., 46: 1116-9, 2003), CEP-7055 (Pro. Am. Assoc. Cancer Research, 43, 1080, 2002, Journal of Medicinal Chemistry., 46: 5375-88, 2003), CP-547,632 (Proc. Am. Soc. Clin. Oncology, 21, (Abstract 16), 2002, Cancer Research. 63:7301-9, 2003, WO 99/62890 ), KRN633 (Pro. Am. Assoc. Cancer Research, 43, 175, 2002, Molecular Cancer Therapeutics., 3:1639-49, 2004), PTK787 (ZK222584) (Cancer Research, 60, 2179-2189, 2000, Journal of Medicinal Chemistry., 43:2310-23, 2000), KRN951, AZD2171 (Cancer Research. 65:4389-400, 2005, WO00/47212 ) and AG013736 (American Journal of Pathology. 165:35-52, 2004) can be prepared in a known manner, for example as described in the respective documents.
    Figure imgb0040
    Figure imgb0041
  • In the present invention, the VEGF receptor kinase inhibitor may also include:
    • (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (hereinafter also referred to as "SU14813"; Proceedings of the American Association for Cancer Research, 46, (Abstract 2031), 2005) (see Formula (XVI)):
      Figure imgb0042
    • (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide (hereinafter also referred to as "OSI930"; Molecular Cancer Therapeutics., 4:1186-1197, 2005) (see Formula (XVII)):
      Figure imgb0043
    • (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one (hereinafter also referred to as "TKI-28"; Cancer Biol Ther., 4, 2005) (see Formula (XVIII)):
      Figure imgb0044
    • (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide (hereinafter also referred to as "ABP309"; EORTC-NCI-AACR Symp Mol Targets Cancer Ther., 2, (Abstract 172), 2004) (see Formula (XEX)):
      Figure imgb0045
    • (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide (hereinafter also referred to as "BAY 57-9352"; International Publication No. WO01/23375 ) (see Formula (XX)):
      Figure imgb0046
    • (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea (hereinafter also referred to as "BAY 43-9006"; Cancer Research., 64, 7099-7109, 2004, Organic Process Res Dev., 6, 777-81, 2002) (see Formula (XXI)):
      Figure imgb0047
    • (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one (hereinafter also referred to as "CHIR258"; Clinical Cancer Research., 11, 3633-3641, 2005) (see Formula (XXII)):
      Figure imgb0048
    • (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile (hereinafter also referred to as "JNJ17029259"; Molecular Pharmacology., 66, 635-647, 2004) (see Formula (XXIII)):
      Figure imgb0049
    • (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine (hereinafter also referred to as "AEE-788"; Cancer Research., 64, 4931-4941, 2004, Cancer Research., 64, 7977-7984, 2004) (see Formula (XXVII)):
      Figure imgb0050
    • (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one (hereinafter also referred to as "CEP-5214"; Journal of Medicinal Chemistry., 46, 5375-5388, 2003., Cancer Research., 63, 5978-5991, 2003) (see Formula (XXVIII)):
      Figure imgb0051
    • (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea (hereinafter also referred to as "KI-8751"; Journal of Medicinal Chemistry., 48, 1359-1366, 2005) (see Formula (XXIX)):
      Figure imgb0052
    • (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid (hereinafter also referred to as "VGA-1155"; Anticancer Research., 24, 3009-3017, 2004) (see Formula (XXX)):
      Figure imgb0053
    • (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea (hereinafter also referred to as "ABT-869"; Proceedings of the American Association for Cancer Research., 46, 1407, (Abstract 5981), 2005) (see Formula (XXXI)):
      Figure imgb0054
    • (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide (hereinafter also referred to as "AG-028262"; WO03/06462 US2004/009965 ) (see Formula (XXXII)):
      Figure imgb0055
    • (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol (hereinafter also referred to as "BMS-540215"; Proceedings of the American Association for Cancer Research., 46, (Abstract 3033), 2005) (see Formula (XXXIII)):
      Figure imgb0056
       and
    • (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate (hereinafter also referred to as "BMS-582664"; Proceedings of the American Association for Cancer Research., 46, (Abstract 3033), 2005) (see Formula (XXXIV)):
      Figure imgb0057
  • SU14813, OSI930, TKI-28, ABP309, BAY 57-9352, BAY 43-9006, CHIR258, JNJ17029259, AEE-788, CEP-5214, KI-8751, VGA-1155, ABT-869, AG-028262, BMS-540215 and BMS-582664 can be prepared in a known manner, for example as described in the respective documents.
  • In the present invention, the VEGF receptor kinase inhibitor may also include, for example, BIBF1120 ( WO01/27081 ), ZK304709 (Proceedings of the American Association for Cancer Research, 46, (Abstract 5842), 2005), Exel7647 (EORTC-NCI-AACR Symp Mol Targets Cancer Ther., (Abstract 134), 2004), AMG706 (EORTC-NCI-AACR Symp Mol Targets Cancer Ther., 2, (Abstract 151), 2004), GW-654652 (Blood.,103, 3474-3479, 2004, Proceedings of the American Association for Cancer Research, 44, 9, (Abstract 39), 2003, Proceedings of the American Association for Cancer Research, 44, 9, (Abstract 40), 2003), and GW-786034 (Proc. Am. Soc. Clin. Oncology, (Abstract 3054), 2004). BIBF1120, ZK304709, Exe17647, AMG706, GW-654652 and GW-786034 can be prepared in a known manner.
  • In the present invention, the VEGF receptor kinase inhibitor may further include, for example, anti-VEGF receptor antibodies. Anti-VEGF receptor antibodies are those having affinity for the VEGF receptor or a fragment thereof. Such anti-VEGF receptor antibodies are preferably neutralizing antibodies that recognize and bind to the VEGF receptor to inhibit the vascular endothelial cell growth activity of VEGF. The anti-VEGF receptor antibodies may be either polyclonal or monoclonal. Also, there is no particularly limitation on the isotypes of the antibodies. The anti-VEGF receptor antibodies may also be either antibody fragments or single chain antibodies (see the section about anti-VEGF antibodies and anti-FGF antibodies described later).
  • The anti-VEGF receptor antibodies may preferably include 2C3 antibody ( US6524583 , US6676941 ), IMC-1121b ( US6811779 ), IMC-18F1 ( Proceedings of the American Association for Cancer Research, 45, 694, (Abstract 3005), 2004), IMC-1C11 ( US5747651 ), and IMC-2C6 (Proceedings of the American Association for Cancer Research, 44, 1479, (Abstract 6454), 2003). These 2C3 antibody, IMC-1121b, IMC-18F1, IMC-1C11 and IMC-2C6 can be prepared in a known manner, for example as described in the respective documents.
    • (2) FGF receptor kinase inhibitors
  • In the present invention, preferred FGF receptor kinase inhibitors are 1-[2-amino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]-3-tert-butylurea (hereinafter also referred to as "PD166866"; J. M. C., 40, 2296-2303, 1997) and 1-tert-butyl-3-[2-(3-dimethylamino)propylamino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]urea (hereinafter also referred to as "PD173074"; EMBO J., 17, 5896-5904, 1998).
  • PD166866 (J. M. C., 40, 2296-2303, 1997) and PD173074 (EMBO J., 17, 5896-5904, 1998) can be prepared in a known manner.
  • Compounds serving as VEGF receptor kinase inhibitors and compounds serving as FGF receptor kinase inhibitors may form pharmacologically acceptable salts with acids or bases. The above receptor kinase inhibitors of the present invention also encompass these pharmacologically acceptable salts. Examples of salts with acids include inorganic acid salts (e.g., hydrochloride salt, hydrobromide salt, sulfate salt, phosphate salt), as well as salts with organic acids such as formic acid, acetic acid, lactic acid, succinic acid, fumaric acid, maleic acid, citric acid, tartaric acid, benzoic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and trifluoroacetic acid. Likewise, examples of salts with bases include alkali metal salts (e.g., sodium salt, potassium salt), alkaline earth metal salts (e.g., calcium salt, magnesium salt), salts with organic bases such as trimethylamine, triethylamine, pyridine, picoline, dicyclohexylamine, N,N'-dibenzylethylenediamine, arginine and lysine (organic amine salts), as well as ammonium salts.
  • Alternatively, compounds serving as VEGF receptor kinase inhibitors and compounds serving as FGF receptor kinase inhibitors may be in anhydride form or may form solvates such as hydrates. Solvates may be either hydrates or anhydrates, preferably hydrates. Solvents available for use include water, alcohols (e.g., methanol, ethanol, n-propanol) and dimethylformamide.
  • In a case where these compounds are present in solvate form and/or have optical isomers, the VEGF receptor kinase inhibitors and FGF receptor kinase inhibitors according to the present invention also encompass their solvates and/or optical isomers. The above receptor kinase inhibitors according to the present invention further encompass VEGF receptor kinase inhibitors and FGF receptor kinase inhibitors that are metabolized in vivo by oxidation, reduction, hydrolysis, conjugation, etc. Furthermore, the above receptor kinase inhibitors according to the present invention encompass compounds that produce VEGF receptor kinase inhibitors and FGF receptor kinase inhibitors when metabolized in vivo by oxidation, reduction, hydrolysis, etc.
    • (3) Anti-VEGF antibodies and anti-FGF antibodies
  • In the present invention, the anti-VEGF antibody is preferably a. neutralizing antibody that recognizes and binds to VEGF to inhibit the vascular endothelial cell growth activity of VEGF.
  • Likewise, in the present invention, the anti-FGF antibody is preferably a neutralizing antibody that recognizes and binds to FGF to inhibit the fibroblast growth activity of FGF.
  • In the present invention, the anti-VEGF antibodies and anti-FGF antibodies may be either polyclonal or monoclonal. Also, there is no particularly limitation on the isotypes of these antibodies; the antibodies may have any isotype, for example, IgG (IgG1, IgG2, IgG3, IgG4), IgM, IgA (IgA1, IgA2), IgD or IgE.
  • Polyclonal and monoclonal antibodies can be prepared in a manner well known to those skilled in the art (Antibodies: A Laboratory Manual, E. Harlow and D. Lane, ed., Cold Spring Harbor Laboratory (Cold Spring Harbor, NY, 1988)).
  • Polyclonal antibodies can be obtained, for example, by administering an antigen to a mammal (e.g., mouse, rabbit, rat), collecting the blood from the mammal, and separating and purifying antibody molecules from the collected blood. Procedures for immunization are known to those skilled in the art and can be accomplished, e.g., by one or more administrations of an antigen. Although an antigen (including a part or all of VEGF or FGF) may be used by being dissolved in an appropriate buffer, for example, containing a commonly-used adjuvant such as complete Freund's adjuvant or aluminum hydroxide, the use of an adjuvant may be eliminated depending on the route of administration or conditions, etc.
  • After 1 to 2 months from the last immunization, the blood may be collected from the mammal and then separated and purified in a routine manner, e.g., by centrifugation, precipitation with ammonium sulfate or polyethylene glycol; or various chromatographic techniques to obtain polyclonal antibodies in the form of a polyclonal antiserum.
  • For monoclonal antibody production, for example, the hybridoma method may be used. As in the case of polyclonal antibody production, a mammal is first immunized. When the appropriate number of days have passed after the immunization, a part of the blood is preferably sampled and measured for its antibody titer in a known manner, e.g., by the ELISA method.
  • The spleen is then isolated from the sensitized and immunized animal to obtain B cells. The B cells are then fused with myeloma cells in a routine manner to create antibody-producing hybridomas. There is no particular limitation on the type of myeloma cells to be used and it is possible to use known types of myeloma cells. For cell fusion, any method known in the art, such as the Sendai virus method, the polyethylene glycol method or the protoplast method, may be selected and used. The resulting hybridomas are cultured in a routine manner in HAT medium (i.e., a medium containing hypoxanthine, aminopterin and thymidine) for an appropriate period of time to effect hybridoma selection. After screening to select a desired antibody-producing hybridoma, the hybridoma is cloned.
  • For screening, it is possible to use any method known for antibody detection, such as the ELISA method or the radioimmunoassay method. For cloning, any method known in the art may be used, including the limiting dilution method and the FACS method. The resulting hybridoma is cultured in an appropriate culture medium or is administered to a mammal (e.g., mouse peritoneal cavity) with which the hybridoma is compatible. From the culture solution or peritoneal fluid thus obtained, a desired monoclonal antibody can be isolated and purified by salting-out, ion exchange chromatography, gel filtration, affinity chromatography, etc.
  • Fragments and V region single chain antibodies of the above antibodies may also be used in the present invention. Such antibody fragments mean partial regions of the above polyclonal or monoclonal antibodies. Specific examples include F(ab')2, Fab', Fab, Fv (variable fragment of antibody), sFv, dsFv (disulphide stabilized Fv) or dAb (single domain antibody). Moreover, the antibodies used in the present invention may also be humanized antibodies or human antibodies. Human antibodies can be created in the same manner as used for standard monoclonal antibody production, except for using a mammal whose immune system is replaced by the human immune system.
    • 3. Pharmaceutical compositions, kits, method for cancer prevention/treatment, and method for angiogenesis inhibition
  • The present invention relates to pharmaceutical compositions, kits, a method for cancer prevention/treatment, and a method for angiogenesis inhibition, which are characterized in that a sulfonamide-including compound is combined with an angiogenesis inhibitor.
  • In the present invention, the sulfonamide-including compound is as described in "1. Sulfonamide-including compounds" and, for example, may be at least one compound selected from (1) a compound of Formula (I), preferably LY186641 or LY295501, (2) a compound of Formula (II), preferably LY-ASAP, (3) LY573636 (Formula (III)), (4) CQS (Formula (IV), and (5) Formula (XIV), preferably E7070 or E7820. The sulfonamide-including compound is more preferably at least one compound selected from LY295501 and LY573636, and particularly preferably a sodium salt of LY573636.
  • Alternatively, in the present invention, the sulfonamide-including compound is preferably E7070 or E7820.
  • In the present invention, the angiogenesis inhibitor is as described in "2. Angiogenesis inhibitors" and, for example, may be (a) a VEGF receptor kinase inhibitor, (b) an anti-VEGF antibody, (c) a FGF receptor kinase inhibitor or (d) an anti-FGF antibody.
  • In the present invention, the VEGF receptor kinase inhibitor (a) may be, for example, a compound represented by at least one selected from Formula (XXIV), Formula (XII), Formula (XIII), Formulae (XVI) to (XXM) and Formulae (XXVII) to (XXXIV). In the present invention, the VEGF receptor kinase inhibitor (a) is preferably a compound of Formula (XXV) or (XXVI), more preferably a compound of Formula (V) or (VI), even more preferably 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide falling within the scope of Formula (V), and particularly preferably a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide. Alternatively, in the present invention, the VEGF receptor kinase inhibitor (a) is preferably a compound represented by at least one selected from Formula (XII), Formula (XIII), Formulae (XVI) to (XXIII) and Formulae (XXVII) to (XXXIV), and more preferably at least one compound selected from KRN951 (Formula (XIII)), AZD2171 (Formula (XIII)), AG013736 (Formula (XIII)), SU14813 (Formula (XVI)), OSI930 (Formula (XVII)), TKI-28 (Formula (XVIII)), ABP309 (Formula (XIX)), BAY 57-9352 (Formula (XX)), BAY 43-9006 (Formula (XXI)), CHIR258 (Formula (XXII)), JNJ17029259 (Formula (XXIII)), AEE-788 (Formula (XXVII)), CEP-5214 (Formula (XXVIII)), KI-8751 (Formula (XXIX)), VGA-1155 (Formula (XXX)), ABT-869 (Formula (XXXI)), AG-028262 (Formula (XXXII)), BMS-540215 (Formula (XXXIII)) and BMS-582664 (Formula (XXXIV)). Alternatively, in the present invention, the VEGF receptor kinase inhibitor (a) may be, for example, an anti-VEGF receptor antibody.
  • In the present invention, the FGF receptor kinase inhibitor (c) is preferably PD166866 or PD 173074.
  • In the present invention, the above compounds and angiogenesis inhibitors also encompass their pharmacologically acceptable salts or solvates (e.g., hydrates) thereof.
  • In the present invention, the sulfonamide compound and the angiogenesis inhibitor may be used in any combination of the above compounds and substances. Such a combination is not limited in any way and may include:
    1. (i) a combination of a compound of Formula (I), a compound of Formula (II), LY573636, CQS or E7070 with an angiogenesis inhibitor;
    2. (ii) a combination of a compound of Formula (XIV) with a VEGF receptor kinase inhibitor; and
    3. (iii) a combination of a compound of Formula (XTV) with an anti-VEGF antibody.
  • The pharmaceutical composition of the present invention comprises a sulfonamide-including compound in combination with an angiogenesis inhibitor. The pharmaceutical composition of the present invention is useful as a pharmaceutical composition for cancer treatment and as a pharmaceutical composition for angiogenesis inhibition.
  • Alternatively, the pharmaceutical composition of the present invention is also provided as another embodiment, i.e., a pharmaceutical composition comprising a sulfonamide-including compound, which is administered together with an angiogenesis inhibitor to a patient. The sulfonamide-including compound and the angiogenesis inhibitor may be administered simultaneously or separately. The term "simultaneously" means that these components are administered at the same timing in a single administration schedule. In this case, it is not necessary to use completely the same hour and minute for administration. The term "separately" means that these components are administered at different timings in a single administration schedule.
  • In the present invention, the phrase "in combination with" means a combination of compounds for combined use, and encompasses both modes in which separate compounds are administered in combination and as a mixture.
  • Likewise, the kit of the present invention comprises a formulation comprising a sulfonamide-including compound and a formulation comprising an angiogenesis inhibitor. The formulations contained in the kit of the present invention may be of any dosage form as long as they contain a sulfonamide-including compound or an angiogenesis inhibitor. The kit of the present invention is useful as a kit for angiogenesis inhibition or as a kit for cancer treatment.
  • The pharmaceutical composition and/or kit of the present invention may further be combined with one or more additional anti-cancer agents. Such additional anti-cancer agents are not limited in any way as long as they are formulations having an anti-cancer effect. Such additional anti-cancer agents include, for example, irinotecan hydrochloride (CPT-11), oxaliplatin, 5-fluorouracil (5-FU), docetaxel (Taxotere®), gemcitabine hydrochloride (Gemzar®), calcium folinate (leucovorin), gefitinib (Iressa®), erlotinib (Tarceva®), and cetuximab (Erbitux®). The above additional anti-cancer agents are particularly preferably irinotecan hydrochloride, oxaliplatin, 5-fluorouracil, calcium folinate, gefitinib, erlotinib and cetuximab in a case where the cancer type targeted by cancer therapeutic agent is colon cancer. Likewise, the above additional anti-cancer agents are particularly preferably gemcitabine hydrochloride, gefitinib, erlotinib and cetuximab for pancreas cancer, and gefitinib, erlotinib and cetuximab for renal cancer.
  • The pharmaceutical composition and/or kit of the present invention can be used as an angiogenesis inhibitory agent or as a cancer therapeutic agent.
  • In the present invention, the term "cancer therapeutic agent" is used to mean an anti-tumor agent, a cancer prognosis improver, a cancer recurrence inhibitor, a cancer metastasis inhibitor, etc.
  • The effect of cancer treatment may be confirmed by findings such as roentgenogram or CT analysis or histopathological diagnosis of biopsy specimens, or alternatively, by tumor marker levels.
  • The pharmaceutical composition and/or kit of the present invention may be administered to mammals (e.g., human, rat, rabbit, sheep, pig, cattle, cat, dog, monkey).
  • The cancer type targeted by cancer therapeutic agent is not limited in any way, and examples include at least one selected from the group consisting of brain tumor, cervical cancer, esophageal cancer, tongue cancer, lung cancer, breast cancer, pancreas cancer, gastric cancer, large intestine cancer, small intestine cancer, duodenal cancer, colon cancer, rectal cancer, bladder cancer, renal cancer, liver cancer, prostate cancer, uterine cancer, ovarian cancer, thyroid gland cancer, gallbladder cancer, pharyngeal cancer, sarcoma (e.g., osteosarcoma, myosarcoma, fibrosarcoma) and melanoma.
  • In the case of using the pharmaceutical composition and/or kit of the present invention, administration may be conducted orally or parenterally.
  • In the case of using the pharmaceutical composition and/or kit of the present invention, the dose of the sulfonamide-including compound will vary depending on the severity of symptoms, the age, sex, body weight and differences in susceptibility of individual patients, the method of administration, the duration of administration, the interval of administration, the nature, pharmacy and type of individual pharmaceutical formulations, as well as the type of active ingredient, etc. Without being particularly limited, the daily dose for adults (body weight: 60 Kg) is usually 10 to 6000 mg, preferably 50 to 4000 mg, and more preferably 100 to 3000 mg, which may usually be given once to three times a day.
  • In the case of using the pharmaceutical composition and/or kit of the present invention, without being particularly limited, the daily adult dose of the VEGF receptor kinase inhibitor is usually 10 to 6000 mg, preferably 50 to 4000 mg, and more preferably 50 to 2000 mg, which may usually be given once to three times a day.
  • Likewise, in the case of using the pharmaceutical composition and/or kit of the present invention, without being particularly limited, the daily adult dose of the FGF receptor kinase inhibitor is usually 10 to 6000 mg, preferably 50 to 4000 mg, and more preferably 50 to 2000 mg, which may usually be given once to three times a day.
  • In the case of using the pharmaceutical composition and/or kit of the present invention, without being particularly limited, the dose of the anti-VEGF antibody is usually 1 to 6000 mg, preferably 10 to 2000 mg, and more preferably 10 to 1000 mg, which may usually be given once to three times a day or a week.
  • In the case of using the pharmaceutical composition and/or kit of the present invention, without being particularly limited, the dose of the anti-FGF antibody is usually 1 to 6000 mg, preferably 10 to 2000 mg, and more preferably 10 to 1000 mg, which may usually be given once to three times a day or a week.
  • The amount of the sulfonamide-including compound to be used is not limited in any way and will vary depending on individual combinations with the VEGF receptor kinase inhibitor, anti-VEGF antibody, FGF receptor kinase inhibitor or anti-FGF antibody. For example, it is about a 0.01- to 100-fold excess (by weight), more preferably about a 0.1- to 10-fold excess (by weight), of the VEGF receptor kinase inhibitor, anti-VEGF antibody, FGF receptor kinase inhibitor or anti-FGF antibody.
  • The pharmaceutical composition of the present invention may be formulated into various dosage forms, for example, oral solid formulations or parenteral formulations including injections, suppositories, ointments and cataplasm.
  • Likewise, the sulfonamide-including compound and the angiogenesis inhibitor contained in the kit of the present invention may each be formulated into various dosage forms, for example, oral solid formulations or parenteral formulations including injections, suppositories, ointments and cataplasm.
  • To prepare oral solid formulations, these active ingredients may be supplemented with excipients and, if necessary, with binders, disintegrating agents, lubricants, coloring agents, flavoring agents and the like, followed by formulation in a routine manner into tablets, coated tablets, granules, fine granules, powders, capsules, etc. It is also possible to prepare oral non-solid formulations such as syrups, when needed.
  • Examples of excipients include lactose, corn starch, sucrose, glucose, sorbit, crystalline cellulose, and silicon dioxide. Examples of binders include polyvinyl alcohol, ethylcellulose, methylcellulose, gum arabic, hydroxypropylcellulose, and hydroxypropylmethylcellulose. Examples of lubricants include magnesium stearate, talc, and silica. Examples of coloring agents include those permitted for use in pharmaceutical preparations. Examples of flavoring agents include cocoa powder, menthol, aromatic acid, peppermint oil, borneol, and cinnamon powder. Of course, tablets and granules may further be coated appropriately with sugar coating, gelatin coating or other coatings, if necessary.
  • To prepare injections, these active ingredients may be supplemented, if necessary, with pH adjustors, buffers, suspending agents, solvent aids, stabilizing agents, isotonizing agents, preservatives and the like, followed by formulation in a routine manner into intravenous injections, subcutaneous injections, intramuscular injections, or intravenous drip infusions. In this case, it is also possible to prepare lyophilized formulations in a routine manner, if necessary.
  • Examples of suspending agents may include methylcellulose, Polysorbate 80, hydroxyethylcellulose, gum arabic, powdered tragacanth, sodium carboxymethylcellulose, and polyoxyethylenesorbitan monolaurate.
  • Examples of solvent aids may include polyoxyethylene hydrogenated castor oil, Polysorbate 80, nicotinamide, polyoxyethylenesorbitan monolaurate, Macrogol, and an ethyl ester of castor oil fatty acid.
  • Likewise, examples of stabilizing agents may include sodium sulfite, and sodium metasulfite. Examples of preservatives may include methyl parahydroxybenzoate, ethyl parahydroxybenzoate, sorbic acid, phenol, cresol, and chlorocresol.
  • In the kit of the present invention, the formulation comprising a sulfonamide-including compound and the formulation comprising an angiogenesis inhibitor may be mixed together or may be included in separate containers and packaged in a single package. These formulations may be administered either simultaneously or sequentially.
  • The kit of the present invention can be used as a kit for angiogenesis inhibition or as a kit for cancer treatment and further comprises a packaging container, an instruction manual, an package insert and the like, in addition to the formulation comprising a sulfonamide-including compound and the formulation comprising an angiogenesis inhibitor. These packaging container, instruction manual and package insert may describe a combination for combined use of the formulations or may describe a dosage regimen for administration of separate formulations in combination or as a mixture, etc. Such a dosage regimen may be described by reference to the above description.
  • In another embodiment, the kit of the present invention may comprise (a) at least one selected from the group consisting of a packaging container, an instruction manual and an package insert, each of which describes the combined use of a sulfonamide-including compound and an angiogenesis inhibitor, and (b) a pharmaceutical composition comprising the sulfonamide-including compound. The kit is useful as a kit for cancer treatment or as a kit for angiogenesis inhibition. The above pharmaceutical composition comprising the sulfonamide-including compound is useful as a pharmaceutical composition for cancer treatment and as a pharmaceutical composition for angiogenesis inhibition. These packaging container, instruction manual and package insert may describe the combined use of the sulfonamide-including compound and the angiogenesis inhibitor or may describe a dosage regimen for administration of separate substances in combination or as a mixture, etc. Such a dosage regimen may be determined by reference to the above description about the pharmaceutical composition/kit.
  • Moreover, the present invention also includes the use of a sulfonamide-including compound for the manufacture of a pharmaceutical composition in combination with an angiogenesis inhibitor.
  • In the use of the present invention, the above pharmaceutical composition is useful as a pharmaceutical composition for cancer treatment and as a pharmaceutical composition for angiogenesis inhibition.
  • Moreover, the present invention also includes a method for preventing or treating cancer or a method for inhibiting angiogenesis, which comprises simultaneously or separately administering a sulfonamide-including compound and an angiogenesis inhibitor to a patient. In the method of the present invention for preventing or treating cancer, there is no particular limitation on the route and method of administration of the sulfonamide-including compound and the angiogenesis inhibitor. With respect to the route and method of administration, reference may be made to the above description about the pharmaceutical composition of the present invention.
  • The present invention will be further described by way of the following illustrative examples, which are not intended to limit the scope of the invention.
    • Example 1 DNA microarray analysis 1) Cell culturing, compound treatment and RNA extraction
  • With the aim of studying compound-induced changes in gene expression by DNA microarray analysis, the human colon cancer cell line HCT116 (American Type Culture Collection, Manassas, VA, U.S.A.) and the human leukemia cell line MOLT-4 (American Type Culture Collection, Manassas, VA, U.S.A.) were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum, 100 units/ml penicillin and 100 µg/ml streptomycin. Hereafter, culturing and compound treatment were carried out in an incubator adjusted to 5% CO2 and 37°C. HCT116 cells and MOLT-4 cells were seeded at a density of 2.0 × 106 cells into cell culture dishes of 10 cm diameter and cultured for 24 hours, followed by compound treatment as shown below.
  • With respect to HCT116 cells, the following 12 compounds were evaluated: E7820 (0.8 µM), E7070 (0.8 µM), LY295501 (30 µM), CQS (8 µM), adriamycin (0.2 µM), daunomycin (0.2 µM), ICRF154 (80 µM), ICRF159 (80 µM), kenpaullone (10 µM), alsterpullone (10 µM), trichostatin A (0.1 µM) and rapamycin (80 µM). On the other hand, with respect to MOLT-4 cells, E7070 (0.8 µM) was evaluated. These compounds are all known compounds, among which adriamycin and daunomycin are known as DNA topoisomerase II inhibitors of DNA intercalation type, ICRF154 and ICRF159 are known as DNA topoisomerase II inhibitors of catalytic type, kenpaullone and alsterpullone are known as cyclin-dependent kinases (CDKs) inhibitors, trichostatin A is known as a histone deacetylase inhibitor, and rapamycin is known as a mTOR/FRAP inhibitor. The treatment concentration of each compound was set to a concentration three to five times higher than the 50% growth inhibitory concentration of each compound against HCT116 cells (based on 3-day cell growth inhibition assays using WST-8). After treatment for 24 hours at the set concentration in parentheses following the name of each compound, the cells were collected. Moreover, the cells cultured for 24 hours in the absence of these compounds were also collected.
  • Extraction of total RNA from the collected cells was performed using a TRIZOL reagent (Invitrogen Corporation) according to the instructions attached thereto.
    • 2) Gene expression analysis by DNA microarrays
  • The resulting RNA was dissolved in 100 µl of diethyl pyrocarbonate (DEPC)-treated sterilized water and further purified using an RNeasy column (QIAGEN), followed by synthesis of double-stranded cDNA using a SuperScript Choice System (Invitrogen Corporation) and a T7-d(T)24 primer.
  • First, 10 µg of RNA was supplemented with 5 µM T7-d(T)24 primer, 1x First strand buffer, 10 mM DTT, 500 µM dNTP mix and 20 units/µl SuperScript II Reverse Transcriptase, and then reacted at 42°C for 1 hour to synthesize single-stranded DNA. Subsequently, 1x Second strand buffer, 200 µM dNTP mix, 67 U/ml DNA ligase, 270 U/ml DNA polymerase I and 13 U/ml RNase H were added and reacted at 16°C for 2 hours to synthesize double-stranded cDNA. Further, 67 U/ml T4 DNA polymerase I was added and reacted at 16°C for 5 minutes, followed by addition of 10 µl of 0.5 M EDTA to stop the reaction.
  • The resulting cDNA was purified by phenol/chloroform and labeled with biotinylated UTP and CTP using an RNA Transcript Labeling Kit (Enzo Diagnostics) according to the instructions attached thereto. The reaction product was purified on an RNeasy column and then heated in 200 mM trisacetic acid pH 8.1, 150 mM magnesium acetate, 50 mM potassium acetate at 94°C for 35 minutes to fragment cRNA.
  • The fragmented cRNA was hybridized to a GeneChip (Affymetrix) Human Focus array in 100 mM MES, 1 M sodium salt, 20 mM EDTA, 0.01% Tween 20 at 45°C for 16 hours. After hybridization, the GeneChip was washed and stained according to the protocol Midi_euk2 attached to an Affymetrix fluidics station. The staining was accomplished by using streptavidin-phycoerythrin and a biotinylated anti-streptavidin goat antibody. The stained GeneChip was scanned with an HP argon ion laser confocal microscope (Hewlett Packard) and measured for fluorescence intensity. The measurement was performed with an excitation wavelength of 488 nm and an emission wavelength of 570 nm.
  • Quantitative data analyses were all conducted by using GeneChip software (Affymetrix) and Gene Spring (Silicongenetics). In the case of using GeneChip software to evaluate compound-induced changes in gene expression, if there is a 2-fold or more difference in the quantified value of RNA between two groups, i.e., compound-treated and untreated groups, it is determined that the expression of a corresponding gene has significantly "increased" or "decreased." In the case of using Gene Spring to evaluate the similarity of changes in gene expression induced by each compound, hierarchical clustering analysis was performed based on changes in the expression of all genes mounted on the Human Focus Arrays.
  • Figure 1 shows the results of hierarchical clustering analysis performed on HCT116 cells.
  • As a result of the analysis, adriamycin and daunomycin, ICRF154 and ICRF159, as well as Kenpaullone and alsterpullone, each pair of which shared the same mechanism of action, were found to cause genetic changes similar to each other (Figure 1). It was therefore confirmed that compounds having the same mechanism of action mutually caused similar genetic changes.
  • E7070, E7820, LY295501 and CQS were found to cause similar genetic changes (Figure 1). Thus, this analysis strongly suggested that E7070, E7820, LY295501 and CQS appeared to have the same or similar mechanism of action and hence produced the same or similar genetic changes and effects.
    • Example 2 DNA microarray analysis
  • In this example, HCT116 cells were used to study changes in gene expression induced by treatment with the following 12 compounds: E7820 (0.16 µM), E7070 (0.26 µM), LY186641 (59 µM), LY295501 (24 µM), LY573636 (9.6 µM), CQS (4.0 µM), MST16 (100 µM), etoposide (3.6 µM), ethoxzolamide (410 µM), capsaicin (280 µM), trichostatin A (0.16 µM) and kenpaullone (7.1 µM).
  • These compounds are all known compounds, among which MST16 is known as a DNA topoisomerase II inhibitor of catalytic type, etoposide is known as a DNA topoisomerase II inhibitor inducing cleavable complex formation, ethoxzolamide is known as a carbonic anhydrase inhibitor, capsaicin is known as a tumor-specific plasma membrane NADH oxidase inhibitor, trichostatin A is known as a histone deacetylase inhibitor, and kenpaullone is known as a cyclin-dependent kinases (CDKs) inhibitor.
  • The treatment concentration of each compound was set to a concentration twice higher than the 50% growth inhibitory concentration of each compound against HCT116 cells (based on 3-day cell growth inhibition assays using MTT). After treatment for 24 hours at the set concentration in parentheses following the name of each compound, the cells were collected. Moreover, the cells cultured for 24 hours in the absence of these compounds were also collected.
  • This example was performed in duplicate for each sample (for experimental convenience, individual samples were subnumbered Control-1, Control-2, E7820-1, E7820-2, etc., such that they could be distinguished from each other). The subsequent procedures were exactly the same as shown in Example 1. Then, a GeneChip (Affymetrix) system (Human Focus array) was used to analyze changes in gene expression induced by each compound.
  • The 26 .cel files obtained in this example for 13 samples (Control + 12 compounds) in duplicate were normalized at the probe level by applying the RMA (robust multi-array average) method (Biostatistics (2003), 4, 249-264), followed by calculating the log value of signal intensity at the gene level. Subsequently, the log value of signal intensity in the untreated group (Control-1) was subtracted from the log value of signal intensity in each compound-treated group for each gene to obtain the log signal ratio of each compound-treated group to Control-1. The cosine correlation coefficient was then calculated and defined as a correlation coefficient between experiments (Figure 2). Based on this correlation coefficient, hierarchical clustering analysis was performed by the UPGMA (Unweighted Pair Group Method with Arithmetic mean) method (Figure 3). The same calculation was also performed on Control-2 (Figures 4 and 5). The software programs used were R 2.0.1 (http://www.r-project.org/) and affy package 1.5.8 (http://www.bioconductor.org).
  • In Figures 2 to 5, "LY1" denotes LY186641, "LY2" denotes LY295501, "LY5" denotes LY573636, "CAI" denotes ethoxzolamide, "Cap" denotes capsaicin, "MST" denotes MST16, "Etop" denotes etoposide, "TSA" denotes trichostatin A, and "Kenp" denotes kenpaullone. In Figures 3 and 5, "de hclust (*, "average")" is a command for statistical analysis and means that the average of duplicate experimental data was used for clustering analysis in R.
  • As a result of the analysis, E7070, E7820, LY186641, LY295501, LY573636 and CQS were found to have a very high similarity in genetic changes caused in HCT116 cells and to have different profiles than any other compounds (MST16, etoposide, ethoxzolamide, capsaicin, trichostatin A, kenpaullone) (Figures 2 to 5). Thus, this analysis strongly suggested that E7070, E7820, LY186641, LY295501, LY573636 and CQS appeared to have the same or similar mechanism of action and hence produced the same or similar genetic changes and effects.
    • Example 3 Cancer cell line panel experiment
  • Panels of 36 human cancer cell lines were used to study the correlation of antiproliferative activity among E7820, E7070, CQS, LY186641 and LY295501. The cancer cell lines used were the following 36 lines: DLD-1, HCT15, HCT116, HT29, SW480, SW620 and WiDr (human colon cancer cell lines), A427, A549, LX-1, NCI-H460, NCI-H522, PC-9 and PC-10 (human lung cancer cell lines), GT3TKB, HGC27; MKN1, MKN7, MKN28 and MKN74 (human stomach cancer cell lines), AsPC-1, KP-1, KP-4, MiaPaCaII, PANC-1 and SUIT-2 (human pancreas cancer cell lines), BSY-1, HBC5, MCF-7, MAD-MB-231, MDA-MB-435 and MDA-MB-468 (human breast cancer cell lines), as well as CCRF-CEM, HL60, K562 and MOLT-4 (human leukemia cell lines). All cells were cultured using RPMI-1640 medium supplemented with 10% fetal bovine serum, 100 units/ml penicillin and 100 µg/ml streptomycin under 5% CO2 conditions at 37°C (Table 1). Table 1
    36 human cancer cell lines tested in 3-day MTT assays
    Colon Stomach Breast
    DLD-1 (1250/well, 16.8 h) GT3TKB (2000/well, 21.1 h) BSY-1 (2000/well, 46.1 h)
    HCT15 (1500/well, 14.5 h) HGC27 (1500/well, 14.6 h) HBC5 (2000/well, 31.8 h)
    HCT116 (1250/well, 13.4 h) MKN1 (4000/well, 35.9 h) MCF-7 (3000/well, 29.5 h)
    HT29 (2500/well, 19.8 h) MKN7 (3000/well, 37.4 h) MDA-MB231 (2000/well, 21.6 h)
    SW480 (3000/well, 19.5 h) MKN28 (2000/well, 22.7 h) MDA-MB-435 (3000/well, 24.4 h)
    SW620 (2500/well, 17.3 h) MKN74 (4000/well, 24.8 h) MDA-MB-468 (3000/well, 34.2 h)
    WiDr (2000/well, 18.9 h)
    Lung Pancreas Leukemia
    A427 (2500/well, 32.4 h) AsPC-1 (2500/well, 28.4 h) CCRF-CEM (1500/well, 27.2 h)
    A549 (1250/well, 18.9 h) KP-1 (2000/well, 24.8 h) HL60 (1500/well, 29.5 h)
    LX-1 (2000/well, 17.2 h) KP-4 (2000/well, 16.7 h) K562 (1500/well, 20.6 h)
    NCI-H460 (1000/well, 13.6 h) MiaPaCaII (2500/well, 19.1 h) MOLT-4 (1500/well, 22.3 h)
    NCI-H522 (4000/well, 80.4 h) PANC-1 (2500/well, 27.9 h)
    PC-9 (2000/well, 23.7 h) SUIT-2 (2000/well, 15.6 h)
    PC-10 (2000/well, 24.0 h)
    Cell line (initial cell number, doubling time)
  • Table 1 shows the type, initial cell number and doubling time of human cancer cell lines in human cancer cell line panels.
  • Cells of these cell lines were seeded in 96-well microplates (flat-bottomed) (50 µl/well) at the cell numbers indicated in Table 1. After 24 hours, a 3-fold dilution series of each compound was added (50 µl/well). After 72 hours, WST-8 (10 µl/well) was further added and the absorbance at 450 nm was measured. The least squares method was used to determine the 50% growth inhibitory concentration of each compound against all 36 cancer cell lines, followed by comparing the pattern of growth inhibition between compounds. As indexes of correlation, Pearson's correlation coefficients were used ( Paull, K. D. et al. Display and analysis of patterns of differential activity of drugs against human tumor cell lines: development of mean graph and COMPARE algorithm. J. Natl. Cancer Inst. 1989, 81, 1088-1092; Monks, A. et al. Feasibility of a high-flux anti-cancer drug screen using a diverse panel of cultured human tumor cell lines. J. Natl. Cancer Inst. 1991, 83, 757-766).
  • As a result, E7070, E7820, LY186641, LY295501. and CQS were found to show high correlation coefficients in antiproliferative activity against each cancer cell line (Table 2). Thus, this analysis strongly suggested that E7070, E7820, LY186641, LY295501 and CQS appeared to have the same or similar mechanism of action and hence produced the same or similar genetic changes and effects. Table 2
    E7070 E7820 CQS LY186641 LY295501
    E7070 1.00 0.98 0.97 0.93 0.80
    E7820 0.98 1.00 0.96 0.95 0.82
    CQS 0.97 0.96 1.00 0.92 0.82
    LY186641 0.93 0.95 0.92 1.00 0.81
    LY295501 0.80 0.82 0.82 0.81 1.00
    Table 2 shows correlation coefficients between compounds (E7070, E7820, CQS, LY186641 and LY295501) in human cancer cell line panels.
    • Example 4 Cross resistance in E7070-resistant sub-clonal cell lines
  • E7070-resistant sub-clonal cell lines were used to evaluate the antiproliferative activity of E7820, LY186641, LY295501, LY-ASAP and CQS. HCT116-C9 was a sub-clone separated from the human colon cancer cell line HCT116 (American Type Culture Collection, Manassas, VA, U.S.A.), while HCT116-C9-C1 and HCT116-C9-C4 were E7070-resistant sub-clonal cell lines obtained by culturing this HCT116-C9 in the presence of gradually increasing concentrations of E7070 (Molecular Cancer Therapeutics, 2002, 1, 275-286).
  • These 3 cell lines HCT116-C9, HCT116-C9-C1 and HCT116-C9-C4 were each seeded at 3000 cells/well in 96-well microplates (flat-bottomed) (50 µl/well). After 24 hours, a 3-fold dilution series of each compound was added (50 µl/well). After 72 hours, the cell growth inhibitory activity was evaluated by the MTT method (Mossmann T., J. Immunol. Methods, 1983, 65, 55-63). The least squares method was used to determine the 50% growth inhibitory concentration of each compound against each cancer cell line.
  • As a result, the antiproliferative activity of E7070 against HCT116-C9 (C9) was IC50 = 0.127 µM, whereas the activity against HCT116-C9-C1 (C9C1) and HCT116-C9-C4 (C9C4) was IC50 = 31.9 µM and 26.9 µM, respectively. It was therefore confirmed that the antiproliferative activity of E7070 against C9C1 and C9C4 was greatly reduced (Figure 6). Likewise, the antiproliferative activity of E7820, CQS, LY186641, LY295501 and LY-ASAP against HCT116-C9 was IC50 = 0.080 µM, 1.73 µM, 33.6 µM, 10.9 µM and 1.63 µM, respectively, whereas the activity against HCT116-C9-C1 and HCT116-C9-C4 was as follows: IC50 = 51.2 µM, 634 µM, 134 µM, 111 µM and 113 µM, respectively, for HCT116-C9-C1 and IC50 = 52.8 µM, 517 µM, 138 µM, 110 µM and 90.3 µM, respectively, for HCT116-C9-C4. Thus, with respect to the antiproliferative activity of E7820, CQS, LY186641, LY295501 and LY-ASAP, a greater reduction in the activity was observed in C9C1 and C9C4 than in C9 (Figure 6). Thus, this strongly suggested that E7070, E7820, LY186641, LY295501, LY-ASAP and CQS appeared to have the same or similar mechanism of action and hence produced the same or similar genetic changes and effects.
    • Example 5 Cross resistance in E7070-resistant sub-clonal cell lines
  • Exactly the same procedure as used in Example 4 was repeated to evaluate the antiproliferative activity of both LY573636 and E7070 using E7070-resistant sub-clonal cell lines.
  • As a result, it was confirmed again that the antiproliferative activity of E7070 was more greatly reduced in HCT116-C9-C 1 and HCT116-C9-C4 (IC50 = 32.7 µM and 28.0 µM, respectively) than in HCT116-C9 (IC50 = 0.127 µM) (Figure 7). Likewise, with respect to the antiproliferative activity of LY573636, a greater reduction in the activity was observed in HCT116-C9-C1 and HCT116-C9-C4 (IC50 = 264 µM and 240 µM, respectively) than in HCT116-C9 (IC50 = 5.11 µM) (Figure 7). Thus, this strongly suggested that LY573636 appeared to have the same or similar mechanism of action as E7070 and hence produced the same or similar genetic changes and effects.
  • These results (Examples 1 to 5) indicated that E7070, E7820, LY186641, LY295501, LY-ASM, LY573636 or CQS or combinations thereof produced the same or similar genetic changes as well as the same or similar actions and effects.
  • Moreover, E7820 has been found to show excellent angiogenesis inhibitory activity and anti-tumor activity when used in combination with an angiogenesis inhibitory agent (see WO03/074045 ).
  • It was therefore indicated that a sulfonamide-including compound, preferably E7070, LY186641, LY295501, LY-ASAP, LY573636 or CQS or combinations thereof, showed excellent angiogenesis inhibitory activity and anti-tumor activity when used in combination with an angiogenesis inhibitor.
    • Example 6 Combined use of E7820 and 4-(3-chloro-4-(cyclopropylaminocarbonyl)-aminophenoxy)-7-methoxy-6-quinolinecarboxamide in subcutaneous transplantation model (in vivo) of human renal cancer cell line 786-O
  • Human renal cancer cell line 786-O (purchased from ATCC) was cultured in RPMI1640 (containing 10% FBS) to about 80% confluency in a 5% carbon dioxide incubator, and the cells were collected by trypsin-EDTA. The cells were diluted with 50% Matrigel-containing phosphate buffer to prepare a 1 × 108 cells/mL suspension, and the resulting cell suspension was subcutaneously transplanted in 0.1 mL volumes to nude mice at the side of their body. Starting from 7 days after the transplantation, E7820 (100 mg/kg, given twice a day for 2 weeks) and 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide (100 mg/kg, given once a day for 2 weeks) were administered alone or in combination by the oral route. Tumor long and short axes were measured with a digimatic caliper (Mitsutoyo) and used to calculate both tumor volume and relative tumor volume according to the following equations. Tumor volume TV = tumor long axis mm × tumor short axis 2 mm 2 / 2
    Figure imgb0058
    • Relative tumor volume RTV = tumor volume at the day of measurement/tumor volume at the first day of administration
  • If the co-treated group shows a statistically significant interaction as analyzed by two-way ANOVA, E7820 and 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide are determined to have a synergistic effect on each other.
  • As a result, E7820 was found to produce a synergistic effect when used in combination with 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, and their combined use showed an excellent anti-tumor effect when compared to the effect of E7820 or 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide alone (Table 3 and Figure 8). Table 3
    Analyte administered Relative tumor volume at Day 22 Mean ± SD Two-way ANOVA
    Control (untreated) 1.61 ± 0.23
    E7820 100 mg/kg 0.80 ± 0.13
    Compound A 100 mg/kg 0.59 ± 0.12
    E7820 100 mg/kg + Compound A 100 mg/kg 0.16 ± 0.02 p < 0.01 Synergistic effect
    Table 3 shows the anti-tumor effect produced by either one or a combination ofE7820
    and 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide (in Table 3 and Figure 8, Compound A denotes 4-(3-chloro-4-(cyclopropylaminocarbonyl)-aminophenoxy)-7-methoxy-6-quinolinecarboxamide) in the transplantation model (in vivo) of renal cancer cell line 786-O. The first day of administration was defined as Day 1.
  • In view of the foregoing, a combination of E7820 and 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide provides pharmaceutical compositions and kits showing excellent anti-tumor activity; the pharmaceutical compositions and kits of the present invention can be used for cancer treatment.
    • INDUSTRIAL APPLICABILITY
  • The present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity.
  • More specifically, as a result of combining sulfonamide-including compounds, preferably E7070, LY186641, LY295501, LY-ASAP, LY573636 or CQS or combinations thereof, with angiogenesis inhibitors, the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity. The pharmaceutical compositions and kits of the present invention are useful for cancer treatment or angiogenesis inhibition. Likewise, when combining sulfonamide-including compounds, preferably E7820, with VEGF receptor kinase inhibitors, the present invention provides pharmaceutical compositions and kits showing excellent angiogenesis inhibitory activity and/or anti-tumor activity. The pharmaceutical compositions and kits of the present invention are useful for cancer treatment or angiogenesis inhibition.

Claims (292)

  1. A pharmaceutical composition comprising a sulfonamide-including compound in combination with an angiogenesis inhibitor,
    wherein the sulfonamide-including compound is at least one compound selected from the group consisting of
    a compound of Formula (I):
    Figure imgb0059
     [wherein E represents -O-, -N(CH3)-, -CH2-, -CH2CH2- or -CH2O-, D represents -CH2- or -O-, R1a represents a hydrogen atom or a halogen atom, and R2a represents a halogen atom or a trifluoromethyl group],
    a compound of Formula (II):
    Figure imgb0060
     [wherein J represents -O- or -NH-, R1b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted C1-4 alkylthio group, an optionally substituted C2-5 alkoxycarbonyl group, a nitro group, an azido group, -O(SO2)CH3, -N(CH3)2, a hydroxyl group, a phenyl group, a substituted phenyl group, a pyridinyl group, a thienyl group, a furyl group, a quinolinyl group or a triazole group, R2b represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-5 alkoxycarbonyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted phenyl group or an optionally substituted quinolinyl group, R3b represents a hydrogen atom or an optionally substituted C1-4 alkoxy group, R4b represents a hydrogen atom or an optionally substituted C1-6 alkyl group (provided that at least one of R3b and R4b is a hydrogen atom), R5b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group or a nitro group, R6b represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group (provided that when R6b is an optionally substituted C1-6 alkyl group, R5b is a hydrogen atom and R7b is a halogen atom), and R7b represents a halogen atom or an optionally substituted C1-6 alkyl group (provided that when either R5b or R7b is an optionally substituted C1-6 alkyl group or when R7b is a halogen atom or an optionally substituted C1-6 alkyl group, either R5b or R6b is a hydrogen atom)],
    a compound of Formula (III):
    Figure imgb0061
     and
    a compound of Formula (IV):
    Figure imgb0062
     or a pharmacologically acceptable salt thereof or a solvate thereof.
  2. The pharmaceutical composition according to claim 1, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of:
    N-[[(4-chlorophenyl)amino]carbonyl]-2,3-dihydro-1H-indene-5-sulfonamide,
    N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide,
    N-(2,4-dichlorobenzoyl)-4-chlorophenylsulfonamide,
    N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, and
    2-sulfanylamido-5-chloroquinoxaline,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  3. The pharmaceutical composition according to claim 1, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide and N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  4. The pharmaceutical composition according to claim 1, wherein the sulfonamide-including compound is a sodium salt of N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide.
  5. A pharmaceutical composition comprising a compound of Formula (IX):
    Figure imgb0063
     or a pharmacologically acceptable salt thereof or a solvate thereof in combination with an angiogenesis inhibitor.
  6. The pharmaceutical composition according to any one of claims 1 to 5, wherein the angiogenesis inhibitor is a VEGF receptor kinase inhibitor.
  7. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXIV):
    Figure imgb0064
     [in Formula (XXIV), Ad represents a group represented by the following formula:
    Figure imgb0065
     (wherein R1d' represents a group represented by the formula -V1-V2-V3 (wherein V1 represents an optionally substituted C1-6 alkylene group; V2 represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6d-, a group represented by the formula -SO2NR6d-, a group represented by the formula -NR6dSO2-, a group represented by the formula -NR6dCO- or a group represented by the formula -NR6d- (wherein R6d represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3 represents a hydrogen atom, an optionally substituted C1-6alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2d' represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVa11Va12 (wherein Va11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Va12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    A1 represents an optionally substituted carbon atom or a nitrogen atom;
    R11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12 represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Va13 represents an oxygen atom or a sulfur atom;
    A11 represents an optionally substituted carbon atom or a nitrogen atom;
    R13 represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group; and
    R14 represents a group represented by the formula -Va14-Va15 (wherein Va14 represents a single bond or a carbonyl group; and Va15 represents a hydrogen atom, a hydroxyl group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, an amino group, an optionally substituted mono-C1-6 alkylamino group, an optionally substituted di-C1-6 alkylamino group, a formyl group, a carboxyl group or an optionally substituted C2-7 alkoxycarbonyl group));
    Xd represents an oxygen atom or a sulfur atom;
    Yd represents a group represented by the following formula:
    Figure imgb0066
     (wherein R3d' represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R7d and R8d each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C1-6 alkylthio group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula - CONVd1Vd2 (wherein Vd1 and Vd2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group);
    R9d represents a hydrogen atom, a halogen atom or a C1-6 alkyl group; and
    W1 and W2 each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R4d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  8. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXV):
    Figure imgb0067
     [in Formula (XXV), R1e represents a group represented by the formula -V1e-V2e-V3e (wherein V1e represents an optionally substituted C1-6 alkylene group; V2e represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6e-, a group represented by the formula -SO2NR6e-, a group represented by the formula -NR6eSO2-, a group represented by the formula -NR6eCO- or a group represented by the formula -NR6e- (wherein R6e represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2e represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    Y1 represents a group represented by the following formula:
    Figure imgb0068
     (wherein R7e and R8e each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe1V2 (wherein Ve1 and Ve2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group); and
    W1e and W2e each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R3e and R4e each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  9. The pharmaceutical composition according to claim 8, wherein R1e is a C1-6 alkyl group (provided that R1e may have one or more substituents selected from the group consisting of a 3- to 10-membered non-aromatic heterocyclic group which may have a C1-6 alkyl group, a hydroxyl group, a C1-6 alkoxy group, an amino group, a mono-C1-6 alkylamino group and a di-C1-6 alkylamino group).
  10. The pharmaceutical composition according to claim 8, wherein R1e is a methyl group or a group represented by the following formula:
    Figure imgb0069
     (wherein Ra3 represents a methyl group; Ra1 represents a hydrogen atom or a hydroxyl group; and Ra2 represents a methoxy group, an ethoxy group, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group).
  11. The pharmaceutical composition according to claim 8, wherein R1e is a methyl group or a 2-methoxyethyl group.
  12. The pharmaceutical composition according to claim 8, wherein R2e is a cyano group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group).
  13. The pharmaceutical composition according to claim 8, wherein R2e is a cyano group or a group represented by the formula -CONHVe16 (wherein Ve16 represents a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group or a C3-8 cycloalkoxy group, provided that Ve16 may have one or more substituents selected from the group consisting of a halogen atom, a cyano group, a hydroxyl group and a C1-6 alkoxy group).
  14. The pharmaceutical composition according to claim 8, wherein R2e is a group represented by the formula -CONHVe17 (wherein Ve17 represents a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group).
  15. The pharmaceutical composition according to claim 8, wherein R2e is a group represented by the formula -CONHVe18 (wherein Ve18 represents a hydrogen atom, a methyl group or a methoxy group).
  16. The pharmaceutical composition according to claim 8, wherein Y1 is a group represented by the following formula:
    Figure imgb0070
     (wherein R71 represents a hydrogen atom or a halogen atom).
  17. The pharmaceutical composition according to claim 8, wherein R3e and R4e are each a hydrogen atom.
  18. The pharmaceutical composition according to claim 8, wherein R5e is a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group or a C6-10 aryl group (provided that R5e may have one or more substituents selected from the group consisting of a halogen atom and a methanesulfonyl group).
  19. The pharmaceutical composition according to claim 8, wherein R5e is a methyl group, an ethyl group or a cyclopropyl group.
  20. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is a compound of Formula (V):
    Figure imgb0071
     [wherein R1c represents a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or a cyclopropyl group, and R2c represents -NH2 or -NHOCH3], or a pharmacologically acceptable salt thereof or a solvate thereof
  21. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-(4-fluorophenyl)urea,
    N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N'-(3-(methylsulfonyl)phenyl)urea,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic acid (2-cyanoethyl)amide, and
    N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  22. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6- , quinolinecarboxamide, and
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  23. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  24. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  25. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXVI):
    Figure imgb0072
     [in Formula (XXVI), R11f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12f represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Vf13 represents an oxygen atom or a sulfur atom;
    A11f represents an optionally substituted carbon atom or a nitrogen atom;
    R4f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R5f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and
    R9f represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  26. The pharmaceutical composition according to claim 25, wherein R11f is an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group.
  27. The pharmaceutical composition according to claim 25, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0073
    Figure imgb0074
     which may have one or more substituents selected from the following substituent group:
    [Substituent group]
    a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0075
    Figure imgb0076
     (wherein RN1 and RN2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group).
  28. The pharmaceutical composition according to claim 25, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0077
  29. The pharmaceutical composition according to claim 25, wherein R12f is a hydrogen atom.
  30. The pharmaceutical composition according to claim 25, wherein Vf13 is an oxygen atom.
  31. The pharmaceutical composition according to claim 25, wherein A11f is a carbon atom.
  32. The pharmaceutical composition according to claim 25, wherein R4f is a hydrogen atom.
  33. The pharmaceutical composition according to claim 25, wherein R5f is a C1-6 alkyl group or a C3-8 cycloalkyl group.
  34. The pharmaceutical composition according to claim 25, wherein R5f is a methyl group.
  35. The pharmaceutical composition according to claim 25, wherein R9f is a hydrogen atom.
  36. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is a compound of Formula (VI):
    Figure imgb0078
     [wherein R1d represents any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0079
    Figure imgb0080
     which may have one or more substituents selected from the substituent group α, and R2d represents -NHR3d (wherein R3d represents a methyl group, an ethyl group or a cyclopropyl group), provided that the substituent group α denotes a group consisting of a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0081
    Figure imgb0082
     (wherein RN1' and RN2' each independently represent a hydrogen atom or a C1-6 alkyl group)], or a pharmacologically acceptable salt thereof or a solvate thereof.
  37. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    5-(2-(((4-hydroxy-4-methylpiperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide,
    N1-methyl-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide,
    N 1-methyl-5-(2-(((4-(piperidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide, and
    N4-(4-(1-(methylamino)carbonyl-1H-5-indolyl)oxy-2-pyridyl)-4-morpholinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  38. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    (1) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]quinazoline-4-amine,
    (2) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline-4-amine,
    (3) 3-[(2,4-dimethylpyrrol-5-yl)methylene]-2-indolinone,
    (4) (Z)-3-(2,4-dimethyl-5-(2-oxo-1,2-dihydroindol-3-ylidenemethyl)-1H-pyrrol-3-yl)-propionic acid,
    (5) 5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide,
    (6) N,N-dimethylglycine 3-{5,6,7,13-tetrahydro-9-[(1-methylethoxy)methyl]-5-oxo-12H-indeno(2,1-a)pyrrolo(3,4-c)carbazol-12-yl}propyl ester,
    (7) 3-(4-bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide,
    (8) N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea,
    (9) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine,
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1- yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oacy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  39. The pharmaceutical composition according to claim 6, wherein the VEGF receptor kinase inhibitor is at least one antibody selected from the group consisting of 2C3 antibody, IMC-1121b, IMC-18F1, IMC-1C11 and IMC-2C6.
  40. The pharmaceutical composition according to any one of claims 1 to 5, wherein the angiogenesis inhibitor is an anti-VEGF antibody.
  41. The pharmaceutical composition according to any one of claims 1 to 5, wherein the angiogenesis inhibitor is a FGF receptor kinase inhibitor.
  42. The pharmaceutical composition according to claim 41, wherein the FGF receptor kinase inhibitor is at least one compound selected from the group consisting of 1-[2-amino-6-(3,5-dimethoacyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]-3-tert-butylurea and 1-tert-butyl-3-[2-(3-dimethylamino)propylamino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]urea, or a pharmacologically acceptable salt thereof or a solvate thereof
  43. The pharmaceutical composition according to any one of claims 1 to 5, wherein the angiogenesis inhibitor is an anti-FGF antibody.
  44. A pharmaceutical composition comprising a sulfonamide-including compound in combination with a VEGF receptor kinase inhibitor,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0083
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0084
     and
    Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinoty!)oxy]phenyt}-N'-(5-methyl-3 - isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1- yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  45. A pharmaceutical composition comprising a sulfonamide-including compound in combination with a VEGF receptor kinase inhibitor,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0085
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0086
     and
    Z represents -N(R2)-
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropyl-aminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  46. The pharmaceutical composition according to claim 45, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylamino-carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  47. The pharmaceutical composition according to any one of claims 44 to 46, wherein the sulfonamide-including compound is N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzene-sulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  48. The pharmaceutical composition according to any one of claims 1, 5, 44 and 45, which is a pharmaceutical composition for cancer treatment.
  49. The pharmaceutical composition according to any one of claims 1, 5, 44 and 45, which is a pharmaceutical composition for angiogenesis inhibition.
  50. A kit comprising:
    (a) at least one selected from the group consisting of a packaging container, an instruction manual and an package insert, each of which describes the combined use of a sulfonamide-including compound and an angiogenesis inhibitor; and
    (b) a pharmaceutical composition comprising the sulfonamide-including compound,
    wherein the sulfonamide-including compound is at least one compound selected from the group consisting of:
    a compound of Formula (I):
    Figure imgb0087
     [wherein E represents -O-, -N(CH3)-, -CH2-, -CH2CH2- or -CH2O- D represents -CH2- or -O-, R1a represents a hydrogen atom or a halogen atom, and R2a represents a halogen atom or a trifluoromethyl group],
    a compound of Formula (II):
    Figure imgb0088
     [wherein J represents -O- or -NH-, R1b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted C1-4 alkylthio group, an optionally substituted C2-5 alkoxycarbonyl group, a nitro group, an azido group, -O(SO2)CH3, -N(CH3)2, a hydroxyl group, a phenyl group, a substituted phenyl group, a pyridinyl group, a thienyl group, a furyl group, a quinolinyl group or a triazole group, R2b represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-5 alkoxycarbonyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted phenyl group or an optionally substituted quinolinyl group, R3b represents a hydrogen atom or an optionally substituted C1-4 alkoxy group, R4b represents a hydrogen atom or an optionally substituted C1-6 alkyl group (provided that at least one of R3b and R4b is a hydrogen atom), R5b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group or a nitro group, R6b represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group (provided that when R6b is an optionally substituted C1-6 alkyl group, R5b is a hydrogen atom and R7b is a halogen atom), and R7b represents a halogen atom or an optionally substituted C1-6 alkyl group (provided that when either R5b or R7b is an optionally substituted C1-6 alkyl group or when R7b is a halogen atom or an optionally substituted C1-6 alkyl group, either R5b or R6b is a hydrogen atom)],
    a compound of Formula (III):
    Figure imgb0089
     and
    a compound of Formula (IV):
    Figure imgb0090
     or a pharmacologically acceptable salt thereof or a solvate thereof.
  51. The kit according to claim 50, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of:
    N-[[(4-chlorophenyl)amino]carbonyl]-2,3-dihydro-1H-indene-5-sulfonamide,
    N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-S-sulfonamide,
    N-(2,4-dichlorobenzoyl)-4-chlorophenylsulfonamide,
    N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, and
    2-sulfanylamido-5-chloroquinoxaline,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  52. The kit according to claim 50, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of N-[[(3,4-dichlorophenyl)-amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide and N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  53. The kit according to claim 50, wherein the sulfonamide-including compound is a sodium salt of N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide.
  54. A kit comprising:
    (a) at least one selected from the group consisting of a packaging container, an instruction manual and an package insert, each of which describes the combined use of a sulfonamide-including compound and an angiogenesis inhibitor; and
    (b) a pharmaceutical composition comprising the sulfonamide-including compound,
    wherein the sulfonamide-including compound is a compound of Formula (IX):
    Figure imgb0091
     or a pharmacologically acceptable salt thereof or a solvate thereof
  55. The kit according to any one of claims 50 to 54, wherein the angiogenesis inhibitor is a VEGF receptor kinase inhibitor.
  56. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXIV):
    Figure imgb0092
     [in Formula (XXIV), Ad represents a group represented by the following formula:
    Figure imgb0093
     (wherein R1d' represents a group represented by the formula -V1-V2-V3 (wherein V1 represents an optionally substituted C1-6 alkylene group; V2 represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6d-, a group represented by the formula -SO2NR6d-, a group represented by the formula -NR6dSO2-, a group represented by the formula -NR6dCO- or a group represented by the formula -NR6d- (wherein R6d represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2d' represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVa11Va12 (wherein Va11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Va12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    A1 represents an optionally substituted carbon atom or a nitrogen atom;
    R11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12 represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Va13 represents an oxygen atom or a sulfur atom;
    A11 represents an optionally substituted carbon atom or a nitrogen atom;
    R13 represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group; and
    R14 represents a group represented by the formula -Va14-Va15 (wherein Va14 represents a single bond or a carbonyl group; and Va15 represents a hydrogen atom, a hydroxyl group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, an amino group, an optionally substituted mono-C1-6 alkylamino group, an optionally substituted di-C1-6 alkylamino group, a formyl group, a carboxyl group or an optionally substituted C2-7 alkoxycarbonyl group));
    Xd represents an oxygen atom or a sulfur atom;
    Yd represents a group represented by the following formula:
    Figure imgb0094
     (wherein R3d' represents a. hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R7d and R8d each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C1-6 alkylthio group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula - CONVd1Vd2 (wherein Vd1 and Vd2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group);
    R9d represents a hydrogen atom, a halogen atom or a C1-6 alkyl group; and
    W1 and W2 each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R4d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  57. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXV):
    Figure imgb0095
     [in Formula (XXV), R1e represents a group represented by the formula -V1e-V2e-V3e (wherein V1e represents an optionally substituted C1-6 alkylene group; V2e represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6e-, a group represented by the formula -SO2NR6e-, a group represented by the formula -NR6eSO2-, a group represented by the formula -NR6eCO- or a group represented by the formula -NR6e- (wherein R6e represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2e represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    Y1 represents a group represented by the following formula:
    Figure imgb0096
     (wherein R7e and R8e each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe1Ve2 (wherein Ve1 and Ve2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group); and
    W1e and W2e each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R3e and R4e each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  58. The kit according to claim 57, wherein R1e is a C1-6 alkyl group (provided that R1e may have one or more substituents selected from the group consisting of a 3- to 10-membered non-aromatic heterocyclic group which may have a C1-6 alkyl group, a hydroxyl group, a C1-6 alkoxy group, an amino group, a mono-C1-6 alkylamino group and a di-C1-6 alkylamino group).
  59. The kit according to claim 57, wherein R1e is a methyl group or a group represented by the following formula:
    Figure imgb0097
     (wherein Ra3 represents a methyl group; Ra1 represents a hydrogen atom or a hydroxyl group; and Ra2 represents a methoxy group, an ethoxy group, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group).
  60. The kit according to claim 57, wherein R1e is a methyl group or a 2-methoxyethyl group.
  61. The kit according to claim 57, wherein R2e is a cyano group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group).
  62. The kit according to claim 57, wherein R2e is a cyano group or a group represented by the formula -CONHVe16 (wherein Ve16 represents a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group or a C3-8 cycloalkoxy group, provided that Ve16 may have one or more substituents selected from the group consisting of a halogen atom, a cyano group, a hydroxyl group and a C1-6 alkoxy group)
  63. The kit according to claim 57, wherein R2e is a group represented by the formula - CONHVe17 (wherein Ve17 represents a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group).
  64. The kit according to claim 57, wherein R2e is a group represented by the formula - CONHVe18 (wherein Ve18 represents a hydrogen atom, a methyl group or a methoxy group).
  65. The kit according to claim 57, wherein Y1 is a group represented by the following formula:
    Figure imgb0098
     (wherein R71 represents a hydrogen atom or a halogen atom).
  66. The kit according to claim 57, wherein R3e and R4e are each a hydrogen atom.
  67. The kit according to claim 57, wherein R5e is a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group or a C6-10 aryl group (provided that R5e may have one or more substituents selected from the group consisting of a halogen atom and a methanesulfonyl group).
  68. The kit according to claim 57, wherein R5e is a methyl group, an ethyl group or a cyclopropyl group.
  69. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is a compound of Formula (V):
    Figure imgb0099
     [wherein R1c represents a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or a cyclopropyl group, and R2c represents -NH2 or -NHOCH3],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  70. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-(4-fluorophenyl)urea,
    N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1 -pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N'-(3-(methylsulfonyl)phenyl)urea,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic acid (2-cyanoethyl)amide, and
    N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  71. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, and
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  72. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  73. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  74. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXVI):
    Figure imgb0100
     [in Formula (XXVI), R11f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12f represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Vf13 represents an oxygen atom or a sulfur atom;
    A11f represents an optionally substituted carbon atom or a nitrogen atom;
    R4f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R5f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and
    R9f represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  75. The kit according to claim 74, wherein R11f is an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group.
  76. The kit according to claim 74, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0101
    Figure imgb0102
     which may have one or more substituents selected from the following substituent group:
    [Substituent group]
    a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0103
    Figure imgb0104
     (wherein RN1 and RN2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group).
  77. The kit according to claim 74, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0105
  78. The kit according to claim 74, wherein R12f is a hydrogen atom.
  79. The kit according to claim 74, wherein Vf13 is an oxygen atom.
  80. The kit according to claim 74, wherein A11f is a carbon atom.
  81. The kit according to claim 74, wherein R4f is a hydrogen atom.
  82. The kit according to claim 74, wherein R5f is a C1-6 alkyl group or a C3-8 cycloalkyl group.
  83. The kit according to claim 74, wherein R5f is a methyl group.
  84. The kit according to claim 74, wherein R9f is a hydrogen atom.
  85. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is a compound of Formula (VI):
    Figure imgb0106
     [wherein R1d represents any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0107
    Figure imgb0108
     which may have one or more substituents selected from the substituent group α, and R2d represents -NHR3d (wherein R3d represents a methyl group, an ethyl group or a cyclopropyl group), provided that the substituent group α denotes a group consisting of a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0109
    Figure imgb0110
     (wherein RN1' and RN2' each independently represent a hydrogen atom or a C1-6 alkyl group)], or a pharmacologically acceptable salt thereof or a solvate thereof.
  86. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    5-(2-(((4-hydroxy-4-methylpiperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide,
    N1-methyl-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(piperidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide, and
    N4-(4-(1-(methylami no)carbonyl-1H-5-indolyl)oxy-2-pyridyl)-4-morpholinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  87. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    (1) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]quinazoline-4-amine,
    (2) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline-4-amine,
    (3) 3-[(2,4-dimethylpyrrol-5-yl)methylene]-2-indolinone,
    (4) (Z)-3-(2,4-dimethyl-5-(2-oxo-1,2-dihydroindol-3-ylidenemethyl)-1H-pyrrol-3-yl)-propionic acid,
    (5) 5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide,
    (6) N,N-dimethylglycine 3-{5,6,7,13-tetrahydro-9-[(1-methylethoxy)methyl]-5-oxo-12H-indeno(2,1-a)pyrrolo(3,4-c)carbazol-12-yl} propyl ester,
    (7) 3-(4-bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide,
    (8) N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea,
    (9) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine,
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pymolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H, 7H, 13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{ 4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indot-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  88. The kit according to claim 55, wherein the VEGF receptor kinase inhibitor is at least one antibody selected from the group consisting of 2C3 antibody, IMC-1121b, IMC-18F1, IMC-1C11 and IMC-2C6.
  89. The kit according to any one of claims 50 to 54, wherein the angiogenesis inhibitor is an anti-VEGF antibody.
  90. The kit according to any one of claims 50 to 54, wherein the angiogenesis inhibitor is a FGF receptor kinase inhibitor.
  91. The kit according to claim 90, wherein the FGF receptor kinase inhibitor is at least one compound selected from the group consisting of 1-[2-amino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]-3-tert-butylurea and 1-tert-butyl-3-[2-(3-dimethylamino)propylamino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-ylJurea, or a pharmacologically acceptable salt thereof or a solvate thereof.
  92. The kit according to any one of claims 50 to 54, wherein the angiogenesis inhibitor is an anti-FGF antibody.
  93. A kit comprising:
    (a) at least one selected from the group consisting of a packaging container, an instruction manual and an package insert, each of which describes the combined use of a sulfonamide-including compound and a VEGF receptor kinase inhibitor; and
    (b) a pharmaceutical composition comprising the sulfonamide-including compound,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0111
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0112
     and
    Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrroto[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  94. A kit comprising:
    (a) at least one selected from the group consisting of a packaging container, an instruction manual and an package insert, each of which describes the combined use of a sulfonamide-including compound and a VEGF receptor kinase inhibitor; and
    (b) a pharmaceutical composition comprising the sulfonamide-including compound,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0113
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0114
     and
    Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  95. The kit according to claim 94, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  96. The kit according to any one of claims 93 to 95, wherein the sulfonamide-including compound is N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  97. The kit according to any one of claims 50, 54, 93 and 94, which is a kit for cancer treatment.
  98. The kit according to any one of claims 50, 54, 93 and 94, which is a kit for angiogenesis inhibition.
  99. A kit comprising a set of a formulation comprising a sulfonamide-including compound and a formulation comprising an angiogenesis inhibitory
    wherein the sulfonamide-including compound is at least one compound selected from the group consisting of
    a compound of Formula (I):
    Figure imgb0115
     [wherein E represents -O-, -N(CH3)-, -CH2-, -CH2CH2- or -CH2O-, D represents -CH2- or -O-, R1a represents a hydrogen atom or a halogen atom, and R2a represents a halogen atom or a trifluoromethyl group],
    a compound of Formula (II):
    Figure imgb0116
     [wherein J represents -O- or -NH-, R1b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted C1-4 alkylthio group, an optionally substituted C2-5 alkoxycarbonyl group, a nitro group, an azido group, -O(SO2)CH3, -N(CH3)2, a hydroxyl group, a phenyl group, a substituted phenyl group, a pyridinyl group, a thienyl group, a furyl group, a quinolinyl group or a triazole group, R2b represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-5 alkoxycarbonyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted phenyl group or an optionally substituted quinolinyl group, R3b represents a hydrogen atom or an optionally substituted C1-4 alkoxy group, R4b represents a hydrogen atom or an optionally substituted C1-6 alkyl group (provided that at least one of R3b and R4b is a hydrogen atom), R5b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group or a nitro group, R6b represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group (provided that when R6b is an optionally substituted C1-6 alkyl group, R5b is a hydrogen atom and R7b is a halogen atom), and R7b represents a halogen atom or an optionally substituted C1-6 alkyl group (provided that when either R5b or R7b is an optionally substituted C1-6 alkyl group or when R7b is a halogen atom or an optionally substituted C1-6 alkyl group, either R5b or R6b is a hydrogen atom)],
    a compound of Formula (III):
    Figure imgb0117
     and
    a compound of Formula (IV):
    Figure imgb0118
     or a pharmacologically acceptable salt thereof or a solvate thereof
  100. The kit according to claim 99, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of:
    N-[[(4-chlorophenyl)amino]carbonyl]-2,3-dihydro-1H-indene-5-sulfonamide,
    N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide,
    N-(2,4-dichlorobenzoyl)-4-chlorophenylsulfonamide,
    N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, and
    2-sulfanylamido-5-chloroquinoxaline,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  101. The kit according to claim 99, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of N-[[(3,4-dichlorophenyl)-amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide and N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  102. The kit according to claim 99, wherein the sulfonamide-including compound is a sodium salt of N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide.
  103. A kit comprising a set of a formulation comprising a compound of Formula (IX):
    Figure imgb0119
     or a pharmacologically acceptable salt thereof or a solvate thereof and a formulation comprising an angiogenesis inhibitor.
  104. The kit according to any one of claims 99 to 103, wherein the angiogenesis inhibitor is a VEGF receptor kinase inhibitor.
  105. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXIV):
    Figure imgb0120
     [in Formula (XXIV), Ad represents a group represented by the following formula:
    Figure imgb0121
     (wherein R1d' represents a group represented by the formula -V1-V2-V3 (wherein V1 represents an optionally substituted C1-6 alkylene group; V2 represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6d-, a group represented by the formula -SO2NR6d-, a group represented by the formula -NR6dSO2-, a group represented by the formula -NR6dCO- or a group represented by the formula -NR6d- (wherein R6d represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2d' represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVa11Va12 (wherein Va11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Va12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    A1 represents an optionally substituted carbon atom or a nitrogen atom;
    R11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12 represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Va13 represents an oxygen atom or a sulfur atom;
    A11 represents an optionally substituted carbon atom or a nitrogen atom;
    R13 represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group; and
    R14 represents a group represented by the formula -Va14-Va15 (wherein Va14 represents a single bond or a carbonyl group; and Va15 represents a hydrogen atom, a hydroxyl group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, an amino group, an optionally substituted mono-C1-6 alkylamino group, an optionally substituted di-C1-6 alkylamino group, a formyl group, a carboxyl group or an optionally substituted C2-7 alkoxycarbonyl group));
    Xd represents an oxygen atom or a sulfur atom;
    Yd represents a group represented by the following formula:
    Figure imgb0122
     (wherein R3d' represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R7d and R8d each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C1-6 alkylthio group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula - CONVd1Vd2 (wherein Vd1 and Vd2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group);
    R9d represents a hydrogen atom, a halogen atom or a C1-6 alkyl group; and
    W1 and W2 each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R4d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  106. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXV):
    Figure imgb0123
     [in Formula (XXV), R1e represents a group represented by the formula -V1e-V2e-V3e (wherein V1e represents an optionally substituted C1-6 alkylene group; V2e represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl' group, a group represented by the formula -CONR6e-, a group represented by the formula -SO2NR6e-, a group represented by the formula -NR6eSO2-, a group represented by the formula -NR6eCO- or a group represented by the formula -NR6e- (wherein R6e represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2e represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    Y1 represents a group represented by the following formula:
    Figure imgb0124
     (wherein R7e and R8e each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe1Ve2 (wherein Ve1 and Ve2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group); and
    W1e and W2e each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R3e and R4e each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  107. The kit according to claim 106, wherein R1e is a C1-6 alkyl group (provided that R1e may have one or more substituents selected from the group consisting of a 3- to 10-membered non-aromatic heterocyclic group which may have a C1-6 alkyl group, a hydroxyl group, a C1-6 alkoxy group, an amino group, a mono-C1-6 alkylamino group and a di-C1-6 alkylamino group).
  108. The kit according to claim 106, wherein R1e is a methyl group or a group represented by the following formula:
    Figure imgb0125
     (wherein Ra3 represents a methyl group; Ra1 represents a hydrogen atom or a hydroxyl group; and Ra2 represents a methoxy group, an ethoxy group, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group).
  109. The kit according to claim 106, wherein R1e is a methyl group or a 2-methoxyethyl group.
  110. The kit according to claim 106, wherein R2e is a cyano group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group).
  111. The kit according to claim 106, wherein R2e is a cyano group or a group represented by the formula -CONHVe16 (wherein Ve16 represents a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group or a C3-8 cycloalkoxy group, provided that Ve16 may have one or more substituents selected from the group consisting of a halogen atom, a cyano group, a hydroxyl group and a C1-6 alkoxy group).
  112. The kit according to claim 106, wherein R2e is a group represented by the formula - CONHVe17 (wherein Ve17 represents a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group).
  113. The kit according to claim 106, wherein R2e is a group represented by the formula - CONHVe18 (wherein Ve18 represents a hydrogen atom, a methyl group or a methoxy group).
  114. The kit according to claim 106, wherein Y1 is a group represented by the following formula:
    Figure imgb0126
     (wherein R71 represents a hydrogen atom or a halogen atom).
  115. The kit according to claim 106, wherein R3e and R4e are each a hydrogen atom.
  116. The kit according to claim 106, wherein R5e is a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group or a C6-10 aryl group (provided that R5e may have one or more substituents selected from the group consisting of a halogen atom and a methanesulfonyl group).
  117. The kit according to claim 106, wherein R5e is a methyl group, an ethyl group or a cyclopropyl group.
  118. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is a compound of Formula (V):
    Figure imgb0127
     [wherein R1c represents a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or a cyclopropyl group, and R2c represents -NH2 or -NHOCH3],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  119. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-(4-fluorophenyl)urea,
    N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocaibonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N'-(3-(methylsulfonyl)phenyl)urea,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic acid (2-cyanoethyl)amide, and
    N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  120. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, and
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  121. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  122. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  123. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXVI):
    Figure imgb0128
     [in Formula (XXVI), R11f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12f represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Vf13 represents an oxygen atom or a sulfur atom;
    A11f represents an optionally substituted carbon atom or a nitrogen atom;
    R4f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R5f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and
    R9f represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  124. The kit according to claim 123, wherein R11f is an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group.
  125. The kit according to claim 123, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0129
    Figure imgb0130
     which may have one or more substituents selected from the following substituent group:
    [Substituent group]
    a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0131
    Figure imgb0132
     (wherein RN1 and RN2 each independently represent a hydrogen atom or an optionally substituted C1-6alkyl group).
  126. The kit according to claim 123, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0133
  127. The kit according to claim 123, wherein R12f is a hydrogen atom.
  128. The kit according to claim 123, wherein Vf13 is an oxygen atom.
  129. The kit according to claim 123, wherein A11f is a carbon atom.
  130. The kit according to claim 123, wherein R4f is a hydrogen atom.
  131. The kit according to claim 123, wherein R5f is a C1-6 alkyl group or a C3-8 cycloalkyl group.
  132. The kit according to claim 123, wherein R5f is a methyl group.
  133. The kit according to claim 123, wherein R9f is a hydrogen atom.
  134. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is a compound of Formula (VI):
    Figure imgb0134
     [wherein R1d represents any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0135
    Figure imgb0136
     which may have one or more substituents selected from the substituent group α, and R2d represents -NHR3d (wherein R3d represents a methyl group, an ethyl group or a cyclopropyl group), provided that the substituent group α denotes a group consisting of a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0137
    Figure imgb0138
     (wherein RN1' and RN2' each independently represent a hydrogen atom or a C1-6 alkyl group)], or a pharmacologically acceptable salt thereof or a solvate thereof
  135. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    5-(2-(((4-hydroxy-4-methylpiperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide,
    N1-methyl-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(piperidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide, and
    N4-(4-(1-(methylamino)carbonyl-1H-5-indolyl)oxy-2-pyridyl)-4-morpholinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  136. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    (1) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]quinazoline-4-amine,
    (2) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline-4-amine,
    (3) 3-[(2,4-dimethylpyrrol-5-yl)methylene]-2-indolinone,
    (4) (Z)-3-(2,4-dimethyl-5-(2-oxo-1,2-dihydroindol-3-ylidenemethyl)-1H-pyrrol-3-yl)-propionic acid,
    (5) 5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide,
    (6) N,N-dimethylglycine 3-{5,6,7,13-tetrahydro-9-[(1-methylethoxy)methyl]-5-oxo-12H-indeno(2, 1-a)pyrrolo(3,4-c)carbazol-12-yl}propyl ester,
    (7) 3-(4-bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide,
    (8) N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea,
    (9) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine,
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'- {4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indot-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  137. The kit according to claim 104, wherein the VEGF receptor kinase inhibitor is at least one antibody selected from the group consisting of 2C3 antibody, IMC-1121b, IMC-18F1, IMC-1C11 and IMC-2C6.
  138. The kit according to any one of claims 99 to 103, wherein the angiogenesis inhibitor is an anti-VEGF antibody.
  139. The kit according to any one of claims 99 to 103, wherein the angiogenesis inhibitor is a FGF receptor kinase inhibitor.
  140. The kit according to claim 139, wherein the FGF receptor kinase inhibitor is at least one compound selected from the group consisting of 1-[2-amino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]-3-tert-butylurea and 1-tert-butyl-3-[2-(3-dimethylamino)propylamino-6-(3,5-dimethoxycyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]urea, or a pharmacologically acceptable salt thereof or a solvate thereof
  141. The kit according to any one of claims 99 to 103, wherein the angiogenesis inhibitor is an anti-FGF antibody.
  142. A kit comprising a set of a formulation comprising a sulfonamide-including compound and a formulation comprising a VEGF receptor kinase inhibitor,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0139
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0140
     and
    Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  143. A kit comprising a set of a formulation comprising a sulfonamide-including compound and a formulation comprising a VEGF receptor kinase inhibitor,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0141
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0142
     and
    Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  144. The kit according to claim 143, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  145. The kit according to any one of claims 142 to 144, wherein the sulfonamide-including compound is N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  146. The kit according to any one of claims 99, 103, 142 and 143, which is a kit for cancer treatment.
  147. The kit according to any one of claims 99, 103, 142 and 143, which is a kit for angiogenesis inhibition.
  148. A method for preventing or treating cancer and/or a method for inhibiting angiogenesis, which comprises administering a sulfonamide-including compound and an angiogenesis inhibitor to a patient,
    wherein the sulfonamide-including compound is at least one compound selected from the group consisting of:
    a compound of Formula (I):
    Figure imgb0143
     [wherein E represents -O-, -N(CH3)-, -CH2-, -CH2CH2- or -CH2O-, D represents -CH2- or -O-, R1a represents a hydrogen atom or a halogen atom, and R2a represents a halogen atom or a trifluoromethyl group],
    a compound of Formula (II):
    Figure imgb0144
     [wherein J represents -O- or -NH-, R1b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted C1-4 alkylthio group, an optionally substituted C2-5 alkoxycarbonyl group, a nitro group, an azido group, -O(SO2)CH3, -N(CH3)2, a hydroxyl group, a phenyl group, a substituted phenyl group, a pyridinyl group, a thienyl group, a furyl group, a quinolinyl group or a triazole group, R2b represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-5 alkoxycarbonyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted phenyl group or an optionally substituted quinolinyl group, R3b represents a hydrogen atom or an optionally substituted C1-4 alkoxy group, R4b represents a hydrogen atom or an optionally substituted C1-6 alkyl group (provided that at least one of R3b and R4b is a hydrogen atom), R5b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group or a nitro group, R6b represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group (provided that when R6b is an optionally substituted C1-6 alkyl group, R5b is a hydrogen atom and R7b is a halogen atom), and R7b represents a halogen atom or an optionally substituted C1-6 alkyl group (provided that when either R5b or R7b is an optionally substituted C1-6 alkyl group or when R7b is a halogen atom or an optionally substituted C1-6 alkyl group, either R5b or R6b is a hydrogen atom)],
    a compound of Formula (III):
    Figure imgb0145
     and
    a compound of Formula (IV):
    Figure imgb0146
     or a pharmacologically acceptable salt thereof or a solvate thereof
  149. The method according to claim 148, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of:
    N-[[(4-chlorophenyl)amino]carbonyl]-2,3-dihydro-1H-indene-5-sulfonamide,
    N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide,
    N-(2,4-dichlorobenzoyl)-4-chlorophenylsulfonamide,
    N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, and
    2-sulfanylamido-5-chloroquinoxaline,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  150. The method according to claim 148, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of N-[[(3,4-dichlorophenyl)-amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide and N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  151. The method according to claim 148, wherein the sulfonamide-including compound is a sodium salt of N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide.
  152. A method for preventing or treating cancer and/or a method for inhibiting angiogenesis, which comprises administering a compound of Formula (IX);
    Figure imgb0147
     or a pharmacologically acceptable salt thereof or a solvate thereof and an angiogenesis inhibitor to a patient.
  153. The method according to any one of claims 148 to 152, wherein the angiogenesis inhibitor is a VEGF receptor kinase inhibitor.
  154. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXTV):
    Figure imgb0148
     [in Formula (XXIV), Ad represents a group represented by the following formula:
    Figure imgb0149
     (wherein R1d' represents a group represented by the formula -V1-V2-V3 (wherein V1 represents an optionally substituted C1-6 alkylene group; V2 represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6d-, a group represented by the formula -SO2NR6d-, a group represented by the formula -NR6dSO2-, a group represented by the formula -NR6dCO- or a group represented by the formula -NR6d- (wherein R6d represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2d' represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVa11Va12 (wherein Va11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Va12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    A1 represents an optionally substituted carbon atom or a nitrogen atom;
    R11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12 represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Va13 represents an oxygen atom or a sulfur atom;
    A11 represents an optionally substituted carbon atom or a nitrogen atom;
    R13 represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group; and
    R14 represents a group represented by the formula -Va14-Va15 (wherein Va14 represents a single bond or a carbonyl group; and Va15 represents a hydrogen atom, a hydroxyl group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, an amino group, an optionally substituted mono-C1-6 alkylamino group, an optionally substituted di-C1-6 alkylamino group, a formyl group, a carboxyl group or an optionally substituted C2-7 alkoxycarbonyl group));
    Xd represents an oxygen atom or a sulfur atom;
    Yd represents a group represented by the following formula:
    Figure imgb0150
     (wherein R3d' represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R7d and R8d each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C1-6 alkylthio group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula - CONVd1Vd2 (wherein Vd1 and Vd2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group);
    R9d represents a hydrogen atom, a halogen atom or a C1-6 alkyl group; and
    W1 and W2 each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R4d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  155. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXV):
    Figure imgb0151
     [in Formula (XXV), R1e represents a group represented by the formula -V1e-V2e-V3e (wherein V1e represents an optionally substituted C1-6 alkylene group; V2e represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group; a sulfonyl group, a group represented by the formula -CONR6e-, a group represented by the formula -SO2NR6e-, a group represented by the formula -NR6eSO2-, a group represented by the formula -NR6eCO- or a group represented by the formula -NR6e- (wherein R6e represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2e represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    Y1 represents a group represented by the following formula:
    Figure imgb0152
     (wherein R7e and R8e each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe1Ve2 (wherein Ve1 and Ve2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group); and
    W1e and W2e each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R3e and R4e each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  156. The method according to claim 155, wherein R1e is a C1-6 alkyl group (provided that R1e may have one or more substituents selected from the group consisting of a 3- to 10-membered non-aromatic heterocyclic group which may have a C1-6 alkyl group, a hydroxyl group, a C1-6 alkoxy group, an amino group, a mono-C1-6 alkylamino group and a di-C1-6 alkylamino group).
  157. The method according to claim 155, wherein R1e is a methyl group or a group represented by the following formula:
    Figure imgb0153
     (wherein Ra3 represents a methyl group; Ra1 represents a hydrogen atom or a hydroxyl group; and Ra2 represents a methoxy group, an ethoxy group, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group).
  158. The method according to claim 155, wherein R1e is a methyl group or a 2-methoxyethyl group.
  159. The method according to claim 155, wherein R2e is a cyano group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group).
  160. The method according to claim 155, wherein R2e is a cyano group or a group represented by the formula -CONHVe16 (wherein Ve16 represents a hydrogen atom, a C1-6alkyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group or a C3-8 cycloalkoxy group, provided that Ve16 may have one or more substituents selected from the group consisting of a halogen atom, a cyano group, a hydroxyl group and a C1-6alkoxy group).
  161. The method according to claim 155, wherein R2e is a group represented by the formula -CONHVe17 (wherein Ve17 represents a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group).
  162. The method according to claim 155, wherein R2e is a group represented by the formula -CONHVe18 (wherein Ve18 represents a hydrogen atom, a methyl group or a methoxy group).
  163. The method according to claim 155, wherein Y1 is a group represented by the following formula:
    Figure imgb0154
     (wherein R71 represents a hydrogen atom or a halogen atom).
  164. The method according to claim 155, wherein R3e and R4e are each a hydrogen atom.
  165. The method according to claim 155, wherein R5e is a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group or a C6-10 aryl group (provided that R5e may have one or more substituents selected from the group consisting of a halogen atom and a methanesulfonyl group).
  166. The method according to claim 155, wherein R5e is a methyl group, an ethyl group or a cyclopropyl group.
  167. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is a compound of Formula (V):
    Figure imgb0155
     [wherein R1c represents a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or a cyclopropyl group, and R2c represents -NH2 or -NHOCH3], or a pharmacologically acceptable salt thereof or a solvate thereof
  168. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-(4-fluorophenyl)urea,
    N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N'-(3-(methylsulfonyl)phenyl)urea,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic acid (2-cyanoethyl)amide, and
    N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  169. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, and
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  170. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  171. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  172. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXVI):
    Figure imgb0156
     [in Formula (XXVI), R11f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12f represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Vf13 represents an oxygen atom or a sulfur atom;
    A11f represents an optionally substituted carbon atom or a nitrogen atom;
    R4f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R5f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and
    R9f represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  173. The method according to claim 172, wherein R11f is an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group.
  174. The method according to claim 172, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0157
    Figure imgb0158
     which may have one or more substituents selected from the following substituent group:
    [Substituent group]
    a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0159
    Figure imgb0160
     (wherein RN1 and RN2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group).
  175. The method according to claim 172, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0161
  176. The method according to claim 172, wherein R12f is a hydrogen atom.
  177. The method according to claim 172, wherein Vf13 is an oxygen atom.
  178. The method according to claim 172, wherein A11f is a carbon atom.
  179. The method according to claim 172, wherein R4f is a hydrogen atom.
  180. The method according to claim 172, wherein R5f is a C1-6 alkyl group or a C3-8 cycloalkyl group.
  181. The method according to claim 172, wherein R5f is a methyl group.
  182. The method according to claim 172, wherein R9f is a hydrogen atom.
  183. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is a compound of Formula (VI):
    Figure imgb0162
     [wherein R1d represents any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0163
    Figure imgb0164
     which may have one or more substituents selected from the substituent group α, and R2d represents -NHR3d (wherein R3d represents a methyl group, an ethyl group or a cyclopropyl group), provided that the substituent group α denotes a group consisting of a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0165
    Figure imgb0166
     (wherein RN1' and RN2' each independently represent a hydrogen atom or a C1-6 alkyl group)], or a pharmacologically acceptable salt thereof or a solvate thereof
  184. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    5-(2-(((4-hydroxy-4-methylpiperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide,
    N1-methyl-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(piperidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide, and
    N4-(4-(1-(methylamino)carbonyl-1H-5-indolyl)oxy-2-pyridyl)-4-morpholinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  185. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    (1) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]quinazoline-4-amine,
    (2) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline-4-amine,
    (3) 3-[(2,4-dimethylpyrrol-5-yl)methylene]-2-indolinone,
    (4) (Z)-3-(2,4-dimethyl-5-(2-oxo-1,2-dihydroindol-3-ylidenemethyl)-1H-pyrrol-3-yl)-propionic acid,
    (5) 5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide,
    (6) N,N-dimethylglycine 3-{5,6,7,13-tetrahydro-9-[(1-methylethoxy)methyl]-5-oxo-12H-indeno(2, 1-a)pyrrolo(3,4-c)carbazol-12-yl}propyl ester,
    (7) 3-(4-bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide,
    (8) N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea,
    (9) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine,
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-(R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  186. The method according to claim 153, wherein the VEGF receptor kinase inhibitor is at least one antibody selected from the group consisting of 2C3 antibody, IMC-1121b, IMC-18F1, IMC-1C11 and IMC-2C6.
  187. The method according to any one of claims 148 to 152, wherein the angiogenesis inhibitor is an anti-VEGF antibody.
  188. The method according to any one of claims 148 to 152, wherein the angiogenesis inhibitor is a FGF receptor kinase inhibitor.
  189. The method according to claim 188, wherein the FGF receptor kinase inhibitor is at least one compound selected from the group consisting of 1-[2-amino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]-3-tert-butylurea and 1-tert-butyl-3-[2-(3-dimethylamino)propylamino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]urea, or a pharmacologically acceptable salt thereof or a solvate thereof
  190. The method according to any one of claims 148 to 152, wherein the angiogenesis inhibitor is an anti-FGF antibody.
  191. A method for preventing or treating cancer and/or a method for inhibiting angiogenesis, which comprises administering a sulfonamide-including compound and a VEGF receptor kinase inhibitor to a patient,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0167
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0168
     and
    Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  192. A method for preventing or treating cancer and/or a method for inhibiting angiogenesis, which comprises administering a sulfonamide-including compound and a VEGF receptor kinase inhibitor to a patient,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0169
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0170
     and
    Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  193. The method according to claim 192, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  194. The method according to any one of claims 191 to 193, wherein the sulfonamide-including compound is N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  195. Use of a sulfonamide-including compound for the manufacture of a pharmaceutical composition in combination with an angiogenesis inhibitor,
    wherein the sulfonamide-including compound is at least one compound selected from the group consisting of:
    a compound of Formula (I):
    Figure imgb0171
     [wherein E represents -O-, -N(CH3)-, -CH2-, -CH2CH2- or -CH2O- D represents -CH2- or -O-, R1a represents a hydrogen atom or a halogen atom, and R2a represents a halogen atom or a trifluoromethyl group],
    a compound of Formula (II):
    Figure imgb0172
     [wherein J represents -O- or -NH-, R1b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted C1-4 alkylthio group, an optionally substituted C2-5 alkoxycarbonyl group, a nitro group, an azido group, -O(SO2)CH3, -N(CH3)2, a hydroxyl group, a phenyl group, a substituted phenyl group, a pyridinyl group, a thienyl group, a furyl group, a quinolinyl group or a triazole group, R2b represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-5 alkoxycarbonyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted phenyl group or an optionally substituted quinolinyl group, R3b represents a hydrogen atom or an optionally substituted C1-4 alkoxy group, R4b represents a hydrogen atom or an optionally substituted C1-6 alkyl group (provided that at least one of R3b and R4b is a hydrogen atom), R5b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group or a nitro group, R6b represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group (provided that when R6b is an optionally substituted C1-6 alkyl group, R5b is a hydrogen atom and R7b is a halogen atom), and R7b represents a halogen atom or an optionally substituted C1-6 alkyl group (provided that when either R5b or R7b is an optionally substituted C1-6 alkyl group or when R7b is a halogen atom or an optionally substituted C1-6 alkyl group, either R5b or R6b is a hydrogen atom)],
    a compound of Formula (III):
    Figure imgb0173
     and
    a compound of Formula (IV):
    Figure imgb0174
     or a pharmacologically acceptable salt thereof or a solvate thereof.
  196. The use according to claim 195, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of
    N-[[(4-chlorophenyl)amino]carbonyl]-2,3-dihydro-1H-indene-5-sulfonamide,
    N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide,
    N-(2,4-dichlorobenzoyl)-4-chlorophenylsulfonamide,
    N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, and
    2-sulfanylamido-5-chloroquinoxaline,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  197. The use according to claim 195, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide and N-(2,4-dichlorobenzoyl)-5-btomothiophene-2-sulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  198. The use according to claim 195, wherein the sulfonamide-including compound is a sodium salt of N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide.
  199. Use of a compound of Formula (IX):
    Figure imgb0175
     or a pharmacologically acceptable salt thereof or a solvate thereof for the manufacture of a pharmaceutical composition in combination with an angiogenesis inhibitor.
  200. The use according to any one of claims 195 to 199, wherein the angiogenesis inhibitor is a VEGF receptor kinase inhibitor.
  201. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXIV):
    Figure imgb0176
     [in Formula (XXIV), Ad represents a group represented by the following formula:
    Figure imgb0177
     (wherein R1d' represents a group represented by the formula -V1-V2-V3 (wherein V1 represents an optionally substituted C1-6 alkylene group; V2 represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6d-, a group represented by the formula -SO2NR6d-, a group represented by the formula -NR6dSO2-, a group represented by the formula -NR6dCO- or a group represented by the formula -NR6d- (wherein R6d represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2d' represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVa11Va12 (wherein Va11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Va12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    A1 represents an optionally substituted carbon atom or a nitrogen atom;
    R11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12 represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Va13 represents an oxygen atom or a sulfur atom;
    A11 represents an optionally substituted carbon atom or a nitrogen atom;
    R13 represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group; and
    R14 represents a group represented by the formula -Va14-Va15 (wherein Va14 represents a single bond or a carbonyl group; and Va15 represents a hydrogen atom, a hydroxyl group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, an amino group, an optionally substituted mono-C1-6 alkylamino group, an optionally substituted di-C1-6 alkylamino group, a formyl group, a carboxyl group or an optionally substituted C2-7 alkoxycarbonyl group));
    Xd represents an oxygen atom or a sulfur atom;
    Yd represents a group represented by the following formula:
    Figure imgb0178
     (wherein R3d' represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R7d and R8d each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C1-6 alkylthio group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula - CONVd1Vd2 (wherein Vd1 and Vd2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group);
    R9d represents a hydrogen atom, a halogen atom or a C1-6 alkyl group; and
    W1 and W2 each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R4d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  202. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXV):
    Figure imgb0179
     [in Formula (XXV), R1e represents a group represented by the formula -V1e-V2e-V3e (wherein V1e represents an optionally substituted C1-6 alkylene group; V2e represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6e-, a group represented by the formula -SO2NR6e-, a group represented by the formula -NR6eSO2-, a group represented by the formula -NR6eCO- or a group represented by the formula -NR6e- (wherein R6e represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2e represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    Y1 represents a group represented by the following formula:
    Figure imgb0180
     (wherein R7e and R8e each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe1Ve2 (wherein Ve1 and Ve2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group); and
    W1e and W2e each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R3e and R4e each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  203. The use according to claim 202, wherein R1e is a C1-6 alkyl group (provided that R1e may have one or more substituents selected from the group consisting of a 3- to 10-membered non-aromatic heterocyclic group which may have a C1-6 alkyl group, a hydroxyl group, a C1-6 alkoxy group, an amino group, a mono-C1-6 alkylamino group and a di-C1-6 alkylamino group).
  204. The use according to claim 202, wherein R1e is a methyl group or a group represented by the following formula:
    Figure imgb0181
     (wherein Ra3 represents a methyl group; Ra1 represents a hydrogen atom or a hydroxyl group; and Ra2 represents a methoxy group, an ethoxy group, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group).
  205. The use according to claim 202, wherein R1e is a methyl group or a 2-methoxyethyl group.
  206. The use according to claim 202, wherein R2e is a cyano group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group).
  207. The use according to claim 202, wherein R2e is a cyano group or a group represented by the formula -CONHVe16 (wherein Ve16 represents a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group or a C3-8 cycloalkoxy group, provided that Ve16 may have one or more substituents selected from the group consisting of a halogen atom, a cyano group, a hydroxyl group and a C1-6 alkoxy group).
  208. The use according to claim 202, wherein R2e is a group represented by the formula - CONHVe17 (wherein Ve17 represents a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group).
  209. The use according to claim 202, wherein R2e is a group represented by the formula - CONHVe18 (wherein Ve18 represents a hydrogen atom, a methyl group or a methoxy group).
  210. The use according to claim 202, wherein Y1 is a group represented by the following formula:
    Figure imgb0182
     (wherein R71 represents a hydrogen atom or a halogen atom).
  211. The use according to claim 202, wherein R3e and R4e are each a hydrogen atom.
  212. The use according to claim 202, wherein R5e is a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group or a C6-10 aryl group (provided that R5e may have one or more substituents selected from the group consisting of a halogen atom and a methanesulfonyl group).
  213. The use according to claim 202, wherein R5e is a methyl group, an ethyl group or a cyclopropyl group.
  214. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is a compound of Formula (V):
    Figure imgb0183
     [wherein R1c represents a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or a cyclopropyl group, and R2c represents -NH2 or -NHOCH3],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  215. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-(4-fluorophenyl)urea,
    N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide,
    4-(4-((cyctopropytamino)carbonyt)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N'-(3-(methylsulfonyl)phenyl)urea,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic acid (2-cyanoethyl)amide, and
    N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  216. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, and
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  217. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  218. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  219. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXVI):
    Figure imgb0184
     [in Formula (XXVI), R11f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12f represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Vf13 represents an oxygen atom or a sulfur atom;
    A11f represents an optionally substituted carbon atom or a nitrogen atom;
    R4f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R5f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and
    R9f represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  220. The use according to claim 219, wherein R11f is an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group.
  221. The use according to claim 219, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0185
    Figure imgb0186
     which may have one or more substituents selected from the following substituent group:
    [Substituent group]
    a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0187
    Figure imgb0188
     (wherein RN1 and RN2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group).
  222. The use according to claim 219, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0189
  223. The use according to claim 219, wherein R12f is a hydrogen atom.
  224. The use according to claim 219, wherein Vf13 is an oxygen atom.
  225. The use according to claim 219, wherein A11f is a carbon atom.
  226. The use according to claim 219, wherein R4f is a hydrogen atom.
  227. The use according to claim 219, wherein R5f is a C1-6 alkyl group or a C3-8 cycloalkyl group.
  228. The use according to claim 219, wherein R5f is a methyl group.
  229. The use according to claim 219, wherein R9f is a hydrogen atom.
  230. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is a compound of Formula (VI):
    Figure imgb0190
     [wherein R1d represents any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0191
    Figure imgb0192
     which may have one or more substituents selected from the substituent group α, and R2d represents -NHR3d (wherein R3d represents a methyl group, an ethyl group or a cyclopropyl group), provided that the substituent group α denotes a group consisting of a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0193
    Figure imgb0194
     (wherein RN1' and RN2' each independently represent a hydrogen atom or a C1-6 alkyl group)],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  231. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    5-(2-(((4-hydroxy-4-methylpiperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide,
    N1-methyl-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(piperidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide, and
    N4-(4-(1-(methylamino)carbonyl-1H-5-indolyl)oxy-2-pyridyl)-4-morpholinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  232. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    (1) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]quinazoline-4-amine,
    (2) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline-4-amine,
    (3) 3-[(2,4-dimethylpyrrol-5-yl)methylene]-2-indolinone,
    (4) (Z)-3-(2,4-dimethyt-5-(2-oxo-1,2-dihydroindol-3-ylidenemethyl)-1H-pyrrol-3-yl)-propionic acid,
    (5) 5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide,
    (6) N,N-dimethylglycine 3-{5,6,7,13-tetrahydro-9-[(1-methylethoxy)methyl]-5-oxo-12H-indeno(2,1-a)pyrrolo(3,4-c)carbazol-12-yl}propyl ester,
    (7) 3-(4-bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide,
    (8) N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea,
    (9) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine,
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H, 7H, 13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) S-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  233. The use according to claim 200, wherein the VEGF receptor kinase inhibitor is at least one antibody selected from the group consisting of 2C3 antibody, IMC-1121b, IMC-18F1, IMC-1C11 and IMC-2C6.
  234. The use according to any one of claims 195 to 199, wherein the angiogenesis inhibitor is an anti-VEGF antibody.
  235. The use according to any one of claims 195 to 199, wherein the angiogenesis inhibitor is a FGF receptor kinase inhibitor.
  236. The use according to claim 235, wherein the FGF receptor kinase inhibitor is at least one compound selected from the group consisting of 1-[2-amino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]-3-tert-butylurea and 1-tert-butyl-3-[2-(3-dimethylamino)propylamino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]urea, or a pharmacologically acceptable salt thereof or a solvate thereof.
  237. The use according to any one of claims 195 to 199, wherein the angiogenesis inhibitor is an anti-FGF antibody.
  238. Use of a sulfonamide-including compound for the manufacture of a pharmaceutical composition in combination with a VEGF receptor kinase inhibitor,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0195
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0196
     and
    Z represents -N(R2)-
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H, 13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  239. Use of a sulfonamide-including compound for the manufacture of a pharmaceutical composition in combination with a VEGF receptor kinase inhibitor,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0197
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0198
     and
    Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  240. The use according to claim 239, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  241. The use according to any one of claims 238 to 240, wherein the sulfonamide-including compound is N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzenesulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  242. The use according to any one of claims 195, 199, 238 and 239, which is a pharmaceutical composition for cancer treatment.
  243. The use according to any one of claims 195, 199, 238 and 239, which is a pharmaceutical composition for angiogenesis inhibition.
  244. A pharmaceutical composition comprising a sulfonamide-including compound, which is administered together with an angiogenesis inhibitor to a patient,
    wherein the sulfonamide-including compound is at least one compound selected from the group consisting of
    a compound of Formula (I):
    Figure imgb0199
     [wherein E represents -O-, -N(CH3)-, -CH2-, -CH2CH2- or -CH2O-, D represents -CH2- or -O-, R1a represents a hydrogen atom or a halogen atom, and R2a represents a halogen atom or a trifluoromethyl group],
    a compound of Formula (II):
    Figure imgb0200
     [wherein J represents -O- or -NH-, R1b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted C1-4 alkylthio group, an optionally substituted C2-5 alkoxycarbonyl group, a nitro group, an azido group, -O(SO2)CH3, -N(CH3)2, a hydroxyl group, a phenyl group, a substituted phenyl group, a pyridinyl group, a thienyl group, a furyl group, a quinolinyl group or a triazole group, R2b represents a hydrogen atom, a halogen atom, a cyano group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-5 alkoxycarbonyl group, an optionally substituted C1-4 alkoxy group, an optionally substituted phenyl group or an optionally substituted quinolinyl group, R3b represents a hydrogen atom or an optionally substituted C1-4 alkoxy group, R4b represents a hydrogen atom or an optionally substituted C1-6 alkyl group (provided that at least one of R3b and R4b is a hydrogen atom), R5b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group or a nitro group, R6b represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group (provided that when R6b is an optionally substituted C1-6 alkyl group, R5b is a hydrogen atom and R7b is a halogen atom), and R7b represents a halogen atom or an optionally substituted C1-6 alkyl group (provided that when either R5b or R7b is an optionally substituted C1-6 alkyl group or when R7b is a halogen atom or an optionally substituted C1-6 alkyl group, either R5b or R6b is a hydrogen atom)],
    a compound of Formula (III):
    Figure imgb0201
     and
    a compound of Formula (IV):
    Figure imgb0202
     or a pharmacologically acceptable salt thereof or a solvate thereof
  245. The pharmaceutical composition according to claim 244, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of:
    N-[[(4-chlorophenyl)amino]carbonyl]-2,3 -dihydro-1H-indene-5-sulfonamide,
    N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide,
    N-(2,4-dichlorobenzoyl)-4-chlorophenylsulfonamide,
    N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, and
    2-sulfanylamido-5-chloroquinoxaline,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  246. The pharmaceutical composition according to claim 244, wherein the sulfonamide-including compound is at least one compound selected from the group consisting of N-[[(3,4-dichlorophenyl)amino]carbonyl]-2,3-dihydrobenzofuran-5-sulfonamide and N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  247. The pharmaceutical composition according to claim 244, wherein the sulfonamide-including compound is a sodium salt of N-(2,4-dichlorobenzoyl)-5-bromothiophene-2-sulfonamide.
  248. A pharmaceutical composition comprising a compound of Formula (IX):
    Figure imgb0203
     or a pharmacologically acceptable salt thereof or a solvate thereof, which is administered together with an angiogenesis inhibitor to a patient.
  249. The pharmaceutical composition according to any one of claims 244 to 248, wherein the angiogenesis inhibitor is a VEGF receptor kinase inhibitor.
  250. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXIV):
    Figure imgb0204
     [in Formula (XXIV), Ad represents a group represented by the following formula:
    Figure imgb0205
     (wherein R1d' represents a group represented by the formula -V1-V2-V3 (wherein V1 represents an optionally substituted C1-6 alkylene group; V2 represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6d-, a group represented by the formula -SO2NR6d-, a group represented by the formula -NR6dSO2-, a group represented by the formula -NR6dCO- or a group represented by the formula -NR6d- (wherein R6d represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2d' represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVa11Va12 (wherein Va11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Va12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    A1 represents an optionally substituted carbon atom or a nitrogen atom;
    R11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12 represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Va13 represents an oxygen atom or a sulfur atom;
    A11 represents an optionally substituted carbon atom or a nitrogen atom;
    R13 represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group; and
    R14 represents a group represented by the formula -Va14-Va15 (wherein Va14 represents a single bond or a carbonyl group; and Va15 represents a hydrogen atom, a hydroxyl group, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, an amino group, an optionally substituted mono-C1-6 alkylamino group, an optionally substituted di-C1-6 alkylamino group, a formyl group, a carboxyl group or an optionally substituted C2-7 alkoxycarbonyl group));
    Xd represents an oxygen atom or a sulfur atom;
    Yd represents a group represented by the following formula:
    Figure imgb0206
     (wherein R3d' represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R7d and R8d each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, an optionally substituted C1-6 alkylthio group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula - CONVd1Vd2 (wherein Vd1 and Vd2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group);
    R9d represents a hydrogen atom, a halogen atom or a C1-6 alkyl group; and
    W1 and W2 each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R4d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5d represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  251. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXV):
    Figure imgb0207
     [in Formula (XXV), R1e represents a group represented by the formula -V1e-V2e-V3e (wherein V1e represents an optionally substituted C1-6 alkylene group; V2e represents a single bond, an oxygen atom, a sulfur atom, a carbonyl group, a sulfinyl group, a sulfonyl group, a group represented by the formula -CONR6e-, a group represented by the formula -SO2NR6e-, a group represented by the formula -NR6eSO2-, a group represented by the formula -NR6eCO- or a group represented by the formula -NR6e- (wherein R6e represents a hydrogen atom, an optionally substituted C1-6 alkyl group or an optionally substituted C3-8 cycloalkyl group); and V3e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group);
    R2e represents a cyano group, an optionally substituted C1-6 alkoxy group, a carboxyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group);
    Y1 represents a group represented by the following formula:
    Figure imgb0208
     (wherein R7e and R8e each independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, an amino group, an optionally substituted C1-6 alkyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C1-6 alkoxy group, a formyl group, an optionally substituted C2-7 acyl group, an optionally substituted C2-7 alkoxycarbonyl group or a group represented by the formula -CONVe1Ve2 (wherein Ve1 and Ve2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group); and
    W1e and W2e each independently represent an optionally substituted carbon atom or a nitrogen atom);
    R3e and R4e each independently represent a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group; and
    R5e represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group],
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  252. The pharmaceutical composition according to claim 251, wherein R1e is a C1-6 alkyl group (provided that R1e may have one or more substituents selected from the group consisting of a 3- to 10-membered non-aromatic heterocyclic group which may have a C1-6 alkyl group, a hydroxyl group, a C1-6 alkoxy group, an amino group, a mono-C1-6 alkylamino group and a di-C1-6 alkylamino group).
  253. The pharmaceutical composition according to claim 251, wherein R1e is a methyl group or a group represented by the following formula:
    Figure imgb0209
     (wherein Ra3 represents a methyl group; Ra1 represents a hydrogen atom or a hydroxyl group; and Ra2 represents a methoxy group, an ethoxy group, a 1-pyrrolidinyl group, a 1-piperidinyl group, a 4-morpholinyl group, a dimethylamino group or a diethylamino group).
  254. The pharmaceutical composition according to claim 251, wherein R1e is a methyl group or a 2-methoxyethyl group.
  255. The pharmaceutical composition according to claim 251, wherein R2e is a cyano group or a group represented by the formula -CONVe11Ve12 (wherein Ve11 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and Ve12 represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group, a hydroxyl group, an optionally substituted C1-6 alkoxy group or an optionally substituted C3-8 cycloalkoxy group).
  256. The pharmaceutical composition according to claim 251, wherein R2e is a cyano group or a group represented by the formula -CONHVe16 (wherein Ve16 represents a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C1-6 alkoxy group or a C3-8 cycloalkoxy group, provided that Ve16 may have one or more substituents selected from the group consisting of a halogen atom, a cyano group, a hydroxyl group and a C1-6 alkoxy group).
  257. The pharmaceutical composition according to claim 251, wherein R2e is a group represented by the formula -CONHVe17 (wherein Ve17 represents a hydrogen atom, a C1-6 alkyl group or a C1-6 alkoxy group).
  258. The pharmaceutical composition according to claim 251, wherein R2e is a group represented by the formula -CONHVe18 (wherein Ve18 represents a hydrogen atom, a methyl group or a methoxy group).
  259. The pharmaceutical composition according to claim 251, wherein Y1 is a group represented by the following formula:
    Figure imgb0210
     (wherein R71 represents a hydrogen atom or a halogen atom).
  260. The pharmaceutical composition according to claim 251, wherein R3e and R4e are each a hydrogen atom.
  261. The pharmaceutical composition according to claim 251, wherein R5e is a hydrogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group or a C6-10 aryl group (provided that R5e may have one or more substituents selected from the group consisting of a halogen atom and a methanesulfonyl group).
  262. The pharmaceutical composition according to claim 251, wherein R5e is a methyl group, an ethyl group or a cyclopropyl group.
  263. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is a compound of Formula (V):
    Figure imgb0211
     [wherein R1c represents a hydrogen atom, a methyl group, an ethyl group, a n-propyl group or a cyclopropyl group, and R2c represents -NH2 or -NHOCH3],
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  264. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-(4-fluorophenyl)urea,
    N-(2-chloro-4-((6-cyano-7-((1-methyl-4-piperidyl)methoxy)-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N-(4-((6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    N-(4-((6-cyano-7-(((2R)-2-hydroxy-3-(1-pyrrolidino)propyl)oxy)-4-quinolyl)oxy)phenyl)-N'-(4-fluorophenyl)urea,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-cyclopropyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-methoxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-fluoroethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-ethyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-hydroxyethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-((2S)-2,3-dihydroxypropyl)oxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-ethoxyethoxy)-6-quinolinecarboxamide,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N-(2-fluoro-4-((6-carbamoyl-7-methoxy-4-quinolyl)oxy)phenyl)-N'-cyclopropylurea,
    N6-(2-hydroxyethyl)-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(1-propylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cis-2-fluoro-cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-(2-methoxyethoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-(2-(4-morpholino)ethoxy)-6-quinolinecarboxamide,
    4-(3-chloro-4-(2-fluoroethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-((2R)tetrahydro-2-furanylmethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-3-diethylamino-2-hydroxypropoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((2R)-2-hydroxy-3-(1-pyrrolidino)propoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N6-methyl-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-((1-methyl-4-piperidyl)methoxy)-6-quinolinecarboxamide,
    N-(4-(6-cyano-7-(2-methoxyethoxy)-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    N-(4-(6-cyano-7-(3-(4-morpholino)propoxy)-4-quinolyl)oxyphenyl)-N'-(3-(methylsulfonyl)phenyl)urea,
    4-(4-((cyclopropylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-fluoro-4-((2-fluoroethylamino)carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-(2-ethoxyethyl)-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(4-(3-ethylureido)-3-fluoro-phenoxy)-7-methoxyquinoline-6-carboxylic acid (2-cyanoethyl)amide, and
    N-(4-(6-(2-cyanoethyl)carbamoyl-7-methoxy-4-quinolyl)oxy-2-fluorophenyl)-N'-cyclopropylurea,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  265. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(ethylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide,
    N6-methoxy-4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    4-(3-chloro-4-(methylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, and
    N6-methoxy-4-(3-chloro-4-(((ethylamino)carbonyl)amino)phenoxy)-7-methoxy-6-quinolinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  266. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof.
  267. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  268. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is a compound of Formula (XXVI):
    Figure imgb0212
     [in Formula (XXVI), R11f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group, an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group;
    R12f represents a hydrogen atom or an optionally substituted C1-6 alkyl group;
    Vf13 represents an oxygen atom or a sulfur atom;
    A11f represents an optionally substituted carbon atom or a nitrogen atom;
    R4f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C2-7 acyl group or an optionally substituted C2-7 alkoxycarbonyl group;
    R5f represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-8 cycloalkyl group, an optionally substituted C6-10 aryl group, an optionally substituted 5- to 10-membered heteroaryl group or an optionally substituted 3- to 10-membered non-aromatic heterocyclic group; and
    R9f represents a hydrogen atom, a halogen atom or an optionally substituted C1-6 alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  269. The pharmaceutical composition according to claim 268, wherein R11f is an optionally substituted 3- to 10-membered non-aromatic heterocyclic group or an optionally substituted mono-C1-6 alkylamino group.
  270. The pharmaceutical composition according to claim 268, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0213
    Figure imgb0214
     which may have one or more substituents selected from the following substituent group:
    [Substituent group]
    a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0215
    Figure imgb0216
     (wherein RN1 and RN2 each independently represent a hydrogen atom or an optionally substituted C1-6 alkyl group).
  271. The pharmaceutical composition according to claim 268, wherein R11f is any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0217
  272. The pharmaceutical composition according to claim 268, wherein R12f is a hydrogen atom.
  273. The pharmaceutical composition according to claim 268, wherein Vf13 is an oxygen atom.
  274. The pharmaceutical composition according to claim 268, wherein A11f is a carbon atom.
  275. The pharmaceutical composition according to claim 268, wherein R4f is a hydrogen atom.
  276. The pharmaceutical composition according to claim 268, wherein R5f is a C1-6 alkyl group or a C3-8 cycloalkyl group.
  277. The pharmaceutical composition according to claim 268, wherein R5f is a methyl group.
  278. The pharmaceutical composition according to claim 268, wherein R9f is a hydrogen atom.
  279. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is a compound of Formula (VI):
    Figure imgb0218
     [wherein R1d represents any one group selected from the group consisting of those represented by the following formulae:
    Figure imgb0219
    Figure imgb0220
     which may have one or more substituents selected from the substituent group α, and R2d represents -NHR3d (wherein R3d represents a methyl group, an ethyl group or a cyclopropyl group), provided that the substituent group α denotes a group consisting of a hydroxyl group, a C1-6 alkyl group, a C3-8 cycloalkyl group, and groups represented by the following formulae:
    Figure imgb0221
    Figure imgb0222
     (wherein RN1' and RN2' each independently represent a hydrogen atom or a C1-6 alkyl group)],
    or a pharmacologically acceptable salt thereof or a solvate thereof
  280. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    5-(2-(((4-hydroxy-4-methylpiperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide,
    N1-methyl-5-(2-((4-hydroxypiperidino)carbonyl)amino-4-pyridyl)oxy-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide,
    N1-methyl-5-(2-(((4-(piperidin-1-yl)piperidin-1-yl)carbonyl)amino)pyridin-4-yloxy)-1H-1-indolecarboxamide, and
    N4-(4-(1-(methylamino)carbonyl-1H-5-indolyl)oxy-2-pyridyl)-4-morpholinecarboxamide,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  281. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of:
    (1) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[2-(1H-1,2,3-triazol-1-yl)ethoxy]quinazoline-4-amine,
    (2) N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazoline-4-amine,
    (3) 3-[(2,4-dimethylpyrrol-5-yl)methylene]-2-indolinone,
    (4) (Z)-3-(2,4-dimethyl-5-(2-oxo-1,2-dihydroindol-3-ylidenemethyl)-1H-pyrrol-3-yl)-propionic acid,
    (5) 5-(5-fluoro-2-oxo-1,2-dihydroindol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide,
    (6) N,N-dimethylglycine 3-{5,6,7,13-tetrahydro-9-[(1-methylethoxy)methyl]-5-oxo-12H-indeno(2,1-a)pyrrolo(3,4-c)carbazol-12-yl}propyl ester,
    (7) 3-(4-bromo-2,6-difluoro-benzyloxy)-5-[3-(4-pyrrolidin-1-yl-butyl)-ureido]-isothiazole-4-carboxylic acid amide,
    (8) N-{2-chloro-4-[(6,7-dimethoxy-4-quinazolinyl)oxy]phenyl}-N'-propylurea,
    (9) 1-(4-chloroanilino)-4-(4-pyridylmethyl)phthalazine,
    (10) N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one;
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3 -d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof.
  282. The pharmaceutical composition according to claim 249, wherein the VEGF receptor kinase inhibitor is at least one antibody selected from the group consisting of 2C3 antibody, IMC-1121b, IMC-18F1, IMC-1C11 and IMC-2C6.
  283. The pharmaceutical composition according to any one of claims 244 to 248, wherein the angiogenesis inhibitor is an anti-VEGF antibody.
  284. The pharmaceutical composition according to any one of claims 244 to 248, wherein the angiogenesis inhibitor is a FGF receptor kinase inhibitor.
  285. The pharmaceutical composition according to claim 284, wherein the FGF receptor kinase inhibitor is at least one compound selected from the group consisting of 1-[2-amino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]-3-tert-butylurea and 1-tert-butyl-3-[2-(3-dimethylamino)propylamino-6-(3,5-dimethoxyphenyl)-pyrido(2,3-d)pyrimidin-7-yl]urea, or a pharmacologically acceptable salt thereof or a solvate thereof
  286. The pharmaceutical composition according to any one of claims 244 to 248, wherein the angiogenesis inhibitor is an anti-FGF antibody.
  287. A pharmaceutical composition comprising a sulfonamide-including compound, which is administered together with a VEGF receptor kinase inhibitor to a patient,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0223
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R1)- or an oxygen atom,
    Y represents:
    Figure imgb0224
     and
    Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is at least one compound selected from the group consisting of
    (10) N-(2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl)-N'-(5-methyl-3-isoxazolyl)urea,
    (11) 4-[(4-fluoro-2-methylindol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline,
    (12) 6-[2-(methylcarbamoyl)phenylsulfanyl]-3-E-[2-(pyridin-2-yl)ethenyl]indazole,
    (13) 5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-((2S)-2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl- 1H-pyrrole-3-carboxamide,
    (14) 3-((quinolin-4-ylmethyl)amino)-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide,
    (15) 6-(2,6-dichlorophenyl)-8-methyl-2-phenylamino-8H-pyrido[2,3-d]pyrimidin-7-one,
    (16) 2-((1,6-dihydro-6-oxo-pyridin-3-ylmethyl)amino)-N-(3-(trifluoromethyl)phenyl)-3-pyridine-carboxamide,
    (17) 4-(4-(4-chloro-phenylamino)-furo[2,3-d]pyridazin-7-yloxymethyl)-pyridine-2-carboxylic acid methylamide,
    (18) N-(3-trifluoromethyl-4-chlorophenyl)-N'-(4-(2-methylcarbamoylpyridin-4-yl)oxyphenyl)urea,
    (19) 4-amino-5-fluoro-3-(6-(4-methyl-piperazin-1-yl)-1H-benzimidazol-2-yl)-1H-quinolin-2-one,
    (20) 4-(4-(1-amino-1-methyl-ethyl)-phenyl)-2-(4-(2-morpholin-4-yl-ethyl)-phenylamino)-pyrimidine-5-carbonitrile,
    (21) [6-[4-[(4-ethylpiperazin-1-yl)methyl]phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-((R)-1-phenylethyl)amine,
    (22) 9-(1-methylethoxy)methyl-12-(3-hydroxypropyl)-6H,7H,13H-indeno[2,1-a]pyrrolo[3,4-c]carbazol-5-one,
    (23) N-(2,4-difluorophenyl)-N'-{4-[(6,7-dimethoxy-4-quinolyl)-oxy]-2-fluorophenyl}urea,
    (24) 5-[N-methyl-N-(4-octadecyloxyphenyl)acetyl]amino-2-methylthiobenzoic acid,
    (25) N-[4-(3-amino-1H-indazol-4-yl)phenyl]-N'-(2-fluoro-5-methylphenyl)urea,
    (26) 2-methyl-6-[2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridin-7-yloxy]-benzo[b]thiophene-3-carboxylic acid methylamide,
    (27) (R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol, and
    (28) (S)-((R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol) 2-aminopropanonate,
    or a pharmacologically acceptable salt thereof or a solvate thereof
  288. A pharmaceutical composition comprising a sulfonamide-including compound, which is administered together with a VEGF receptor kinase inhibitor a patient,
    wherein the sulfonamide-including compound is a compound of Formula (XIV):
    Figure imgb0225
     [wherein
    the ring A represents an optionally substituted monocyclic or bicyclic aromatic ring,
    the ring B represents an optionally substituted 6-membered cyclic unsaturated hydrocarbon or an optionally substituted unsaturated 6-membered heterocyclic ring containing one nitrogen atom as a heteroatom,
    the ring C represents an optionally substituted 5-membered heterocyclic ring containing one or two nitrogen atoms,
    W represents a single bond or -CH=CH-,
    X represents -N(R')- or an oxygen atom,
    Y represents:
    Figure imgb0226
     and
    Z represents -N(R2)-,
    wherein R1, R2 and R3, which may be the same or different, each independently represent a hydrogen atom or a lower alkyl group],
    or a pharmacologically acceptable salt thereof or a solvate thereof, and
    wherein the VEGF receptor kinase inhibitor is 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  289. The pharmaceutical composition according to claim 288, wherein the VEGF receptor kinase inhibitor is a methanesulfonate salt of 4-(3-chloro-4-(cyclopropylamino-carbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide.
  290. The pharmaceutical composition according to any one of claims 287 to 289, wherein the sulfonamide-including compound is N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzene-sulfonamide, or a pharmacologically acceptable salt thereof or a solvate thereof
  291. The pharmaceutical composition according to any one of claims 244, 248, 287 and 288, which is a pharmaceutical composition for cancer treatment.
  292. The pharmaceutical composition according to any one of claims 244, 248, 287 and 288, which is a pharmaceutical composition for angiogenesis inhibition.
EP05785820A 2004-09-13 2005-09-13 Joint use of sulfonamide based compound with angiogenesis inhibitor Withdrawn EP1797877A4 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP11169343A EP2364699A1 (en) 2004-09-13 2005-09-13 Joint use of sulfonamide based compound with angiogenesis inhibitor

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US60945204P 2004-09-13 2004-09-13
JP2005054475 2005-02-28
JP2005054150 2005-02-28
PCT/JP2005/017238 WO2006030947A1 (en) 2004-09-13 2005-09-13 Joint use of sulfonamide based compound with angiogenesis inhibitor

Publications (2)

Publication Number Publication Date
EP1797877A1 true EP1797877A1 (en) 2007-06-20
EP1797877A4 EP1797877A4 (en) 2010-12-15

Family

ID=36060184

Family Applications (2)

Application Number Title Priority Date Filing Date
EP05785820A Withdrawn EP1797877A4 (en) 2004-09-13 2005-09-13 Joint use of sulfonamide based compound with angiogenesis inhibitor
EP11169343A Withdrawn EP2364699A1 (en) 2004-09-13 2005-09-13 Joint use of sulfonamide based compound with angiogenesis inhibitor

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP11169343A Withdrawn EP2364699A1 (en) 2004-09-13 2005-09-13 Joint use of sulfonamide based compound with angiogenesis inhibitor

Country Status (2)

Country Link
EP (2) EP1797877A4 (en)
WO (2) WO2006030947A1 (en)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007115286A2 (en) * 2006-04-05 2007-10-11 Novartis Ag. Combinations of therapeutic agents for treating cancer
EP1481678A4 (en) * 2002-03-05 2009-12-30 Eisai R&D Man Co Ltd Antitumor agent comprising combination of sulfonamide-containing heterocyclic compound with angiogenesis inhibitor
US7973160B2 (en) 2000-10-20 2011-07-05 Eisai R&D Management Co., Ltd. Nitrogen-containing aromatic derivatives
US8058474B2 (en) 2003-11-11 2011-11-15 Eisai R&D Management Co., Ltd. Urea derivative and process for preparing the same
US8865737B2 (en) 2006-08-28 2014-10-21 Eisai R&D Management Co., Ltd. Antitumor agent for undifferentiated gastric cancer
US8962655B2 (en) 2007-01-29 2015-02-24 Eisai R&D Management Co., Ltd. Composition for treatment of undifferentiated gastric cancer
US8969379B2 (en) 2004-09-17 2015-03-03 Eisai R&D Management Co., Ltd. Pharmaceutical compositions of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7=methoxy-6-quinolinecarboxide
US8969344B2 (en) 2005-08-02 2015-03-03 Eisai R&D Management Co., Ltd. Method for assay on the effect of vascularization inhibitor
US9006256B2 (en) 2006-05-18 2015-04-14 Eisai R&D Management Co., Ltd. Antitumor agent for thyroid cancer
US9012458B2 (en) 2010-06-25 2015-04-21 Eisai R&D Management Co., Ltd. Antitumor agent using compounds having kinase inhibitory effect in combination
US9334239B2 (en) 2012-12-21 2016-05-10 Eisai R&D Management Co., Ltd. Amorphous form of quinoline derivative, and method for producing same
US9945862B2 (en) 2011-06-03 2018-04-17 Eisai R&D Management Co., Ltd. Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds
US10259791B2 (en) 2014-08-28 2019-04-16 Eisai R&D Management Co., Ltd. High-purity quinoline derivative and method for manufacturing same
US10517861B2 (en) 2013-05-14 2019-12-31 Eisai R&D Management Co., Ltd. Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds
US11090386B2 (en) 2015-02-25 2021-08-17 Eisai R&D Management Co., Ltd. Method for suppressing bitterness of quinoline derivative
US11369623B2 (en) 2015-06-16 2022-06-28 Prism Pharma Co., Ltd. Anticancer combination of a CBP/catenin inhibitor and an immune checkpoint inhibitor
US11547705B2 (en) 2015-03-04 2023-01-10 Merck Sharp & Dohme Llc Combination of a PD-1 antagonist and a VEGF-R/FGFR/RET tyrosine kinase inhibitor for treating cancer

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1604665B1 (en) 2003-03-10 2011-05-11 Eisai R&D Management Co., Ltd. C-kit kinase inhibitor
WO2006090928A1 (en) * 2005-02-28 2006-08-31 Eisai R & D Management Co., Ltd. Novel use of sulfonamide compound in combination with angiogenesis inhibitor
DK1859793T3 (en) * 2005-02-28 2011-08-01 Eisai R&D Man Co Ltd Hitherto unknown combination use of a sulfonamide compound in the treatment of cancer
US20090047365A1 (en) * 2005-02-28 2009-02-19 Eisai R & D Management Co., Ltd. Novel Concomitant Use of Sulfonamide Compound with Anti-Cancer Agent
WO2007038648A1 (en) * 2005-09-27 2007-04-05 Bristol-Myers Squibb Company Crystalline forms of [(1r), 2s]-2-aminopropionic acid 2-[4-(4-fluoro-2-methyl-1h-indol-5-yloxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yloxy]-1-methylethyl ester
JPWO2007052849A1 (en) 2005-11-07 2009-04-30 エーザイ・アール・アンド・ディー・マネジメント株式会社 Combination use of angiogenesis inhibitor and c-kit kinase inhibitor
EP2015070A4 (en) 2006-04-20 2010-04-21 Eisai R&D Man Co Ltd Novel marker for sensitivity against sulfonamide compound
AU2008325608B2 (en) 2007-11-09 2013-03-14 Eisai R & D Management Co., Ltd. Combination of anti-angiogenic substance and anti-tumor platinum complex
WO2010071885A1 (en) 2008-12-19 2010-06-24 Cephalon, Inc. Pyrrolotriazines as alk and jak2 inhibitors
AU2012246490B2 (en) 2011-04-18 2016-08-04 Eisai R&D Management Co., Ltd. Therapeutic agent for tumor
EP2956138B1 (en) 2013-02-15 2022-06-22 Kala Pharmaceuticals, Inc. Therapeutic compounds and uses thereof
US9688688B2 (en) 2013-02-20 2017-06-27 Kala Pharmaceuticals, Inc. Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof
CN107915751A (en) 2013-02-20 2018-04-17 卡拉制药公司 Therapeutic compound and its purposes
WO2015066482A1 (en) 2013-11-01 2015-05-07 Kala Pharmaceuticals, Inc. Crystalline forms of therapeutic compounds and uses thereof
US9890173B2 (en) 2013-11-01 2018-02-13 Kala Pharmaceuticals, Inc. Crystalline forms of therapeutic compounds and uses thereof
JP2017206437A (en) * 2014-08-18 2017-11-24 エーザイ・アール・アンド・ディー・マネジメント株式会社 4-aminopyridine derivative
CA3036340A1 (en) 2016-09-08 2018-03-15 Kala Pharmaceuticals, Inc. Crystalline forms of therapeutic compounds and uses thereof
US10253036B2 (en) 2016-09-08 2019-04-09 Kala Pharmaceuticals, Inc. Crystalline forms of therapeutic compounds and uses thereof
EP3509421A4 (en) 2016-09-08 2020-05-20 Kala Pharmaceuticals, Inc. Crystalline forms of therapeutic compounds and uses thereof
AU2023242146A1 (en) * 2022-03-31 2024-09-05 Eisai R&D Management Co., Ltd. Liposome composition and liposome-containing pharmaceutical composition

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0222475A1 (en) * 1985-09-23 1987-05-20 Eli Lilly And Company Sulfonyl ureas with anti-tumour activity
EP0555036A2 (en) * 1992-02-05 1993-08-11 Eli Lilly And Company Antitumor compositions and methods of treatment
WO2003074045A1 (en) * 2002-03-05 2003-09-12 Eisai Co., Ltd. Antitumor agent comprising combination of sulfonamide-containing heterocyclic compound with angiogenesis inhibitor

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5367057A (en) 1991-04-02 1994-11-22 The Trustees Of Princeton University Tyrosine kinase receptor flk-2 and fragments thereof
JP3545461B2 (en) 1993-09-10 2004-07-21 エーザイ株式会社 Bicyclic heterocycle-containing sulfonamide derivatives
ES2206469T3 (en) 1993-09-10 2004-05-16 Eisai Co., Ltd. BICYCLIC HETEROCICLIC DERIVATIVES OF SULFONAMIDE AND SULFONIC ESTER
US6811779B2 (en) 1994-02-10 2004-11-02 Imclone Systems Incorporated Methods for reducing tumor growth with VEGF receptor antibody combined with radiation and chemotherapy
US5880141A (en) 1995-06-07 1999-03-09 Sugen, Inc. Benzylidene-Z-indoline compounds for the treatment of disease
CO4950519A1 (en) 1997-02-13 2000-09-01 Novartis Ag PHTHALAZINES, PHARMACEUTICAL PREPARATIONS THAT UNDERSTAND THEM AND THE PROCESS FOR THEIR PREPARATION
UA60365C2 (en) 1998-06-04 2003-10-15 Пфайзер Продактс Інк. Isothiazole derivatives, a method for preparing thereof, a pharmaceutical composition and a method for treatment of hyperproliferative disease of mammal
IL144745A0 (en) 1999-02-10 2002-06-30 Astrazeneca Ab Quinazoline derivatives as angiogenesis inhibitors
JP2000247949A (en) 1999-02-26 2000-09-12 Eisai Co Ltd Indole compound containing sulfonamide
NZ514918A (en) 1999-04-28 2003-11-28 Univ Texas Compositions and methods for cancer treatment by selectively inhibiting VEGF
AR025752A1 (en) 1999-09-28 2002-12-11 Bayer Corp PIRIDINES AND REPLACED PIRIDACINES WITH ANGIOGENESIS INHIBITION ACTIVITY
UA75054C2 (en) 1999-10-13 2006-03-15 Бьорінгер Інгельхайм Фарма Гмбх & Ко. Кг Substituted in position 6 indolinones, producing and use thereof as medicament
AU9598601A (en) 2000-10-20 2002-04-29 Eisai Co Ltd Nitrogenous aromatic ring compounds
SK14642003A3 (en) * 2001-06-06 2004-12-01 Eli Lilly And Company Benzoylsulfonamides and sulfonylbenzamidines for use as anti-tumour agents
GB0117144D0 (en) 2001-07-13 2001-09-05 Glaxo Group Ltd Process
TWI281916B (en) * 2001-10-25 2007-06-01 Lilly Co Eli Antitumor compounds and methods
UA77303C2 (en) 2002-06-14 2006-11-15 Pfizer Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use
EP1522540A4 (en) 2002-08-30 2011-08-10 Eisai R&D Man Co Ltd Azaarene derivatives
AU2004309217B2 (en) 2003-12-25 2008-11-06 Eisai R&D Management Co., Ltd Crystal of salt of 4-(3-chloro-4-(cyclopropylaminocarbonyl)amino-phenoxy)-7-methoxy-6-quinolinecarboxamide or of solvate thereof and processes for producing these

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0222475A1 (en) * 1985-09-23 1987-05-20 Eli Lilly And Company Sulfonyl ureas with anti-tumour activity
EP0555036A2 (en) * 1992-02-05 1993-08-11 Eli Lilly And Company Antitumor compositions and methods of treatment
WO2003074045A1 (en) * 2002-03-05 2003-09-12 Eisai Co., Ltd. Antitumor agent comprising combination of sulfonamide-containing heterocyclic compound with angiogenesis inhibitor

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
FOSSELLA F V ET AL: "Hypoprothrombinemia from coadministration of sulofenur (LY 186641) and warfarin: Report of three cases" INVESTIGATIONAL NEW DRUGS 1991 US, vol. 9, no. 4, 1991, pages 357-359, XP008128554 ISSN: 0167-6997 *
MOUSA SHAKER A: "Anticoagulants in thrombosis and cancer: The missing link" SEMINARS IN THROMBOSIS AND HEMOSTASIS, vol. 28, no. 1, February 2002 (2002-02), pages 45-52, XP002607969 ISSN: 0094-6176 *
ONO NAOTO ET AL: "Angiogenesis inhibitor, E7820; enhancement of anti-angiogenic activity through the combination with receptor kinase inhibitors of VEGF or bFGF" PROCEEDINGS OF THE ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, AMERICAN ASSOCIATION FOR CANCER RESEARCH, US, vol. 43, 1 March 2002 (2002-03-01), page 182, XP001538359 ISSN: 0197-016X *
See also references of WO2006030947A1 *

Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7973160B2 (en) 2000-10-20 2011-07-05 Eisai R&D Management Co., Ltd. Nitrogen-containing aromatic derivatives
US8372981B2 (en) 2000-10-20 2013-02-12 Eisai R&D Management Co., Ltd. Nitrogen-containing aromatic derivatives
EP1481678A4 (en) * 2002-03-05 2009-12-30 Eisai R&D Man Co Ltd Antitumor agent comprising combination of sulfonamide-containing heterocyclic compound with angiogenesis inhibitor
US8058474B2 (en) 2003-11-11 2011-11-15 Eisai R&D Management Co., Ltd. Urea derivative and process for preparing the same
US8969379B2 (en) 2004-09-17 2015-03-03 Eisai R&D Management Co., Ltd. Pharmaceutical compositions of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7=methoxy-6-quinolinecarboxide
US9504746B2 (en) 2004-09-17 2016-11-29 Eisai R&D Management Co., Ltd. Pharmaceutical compositions of 4-(3-chloro-4-(cyclopropylaminocarbonyl)aminophenoxy)-7-methoxy-6-quinolinecarboxamide
US8969344B2 (en) 2005-08-02 2015-03-03 Eisai R&D Management Co., Ltd. Method for assay on the effect of vascularization inhibitor
US9006240B2 (en) 2005-08-02 2015-04-14 Eisai R&D Management Co., Ltd. Method for assay on the effect of vascularization inhibitor
WO2007115286A3 (en) * 2006-04-05 2008-04-17 Novartis Ag Combinations of therapeutic agents for treating cancer
WO2007115286A2 (en) * 2006-04-05 2007-10-11 Novartis Ag. Combinations of therapeutic agents for treating cancer
US9006256B2 (en) 2006-05-18 2015-04-14 Eisai R&D Management Co., Ltd. Antitumor agent for thyroid cancer
US8865737B2 (en) 2006-08-28 2014-10-21 Eisai R&D Management Co., Ltd. Antitumor agent for undifferentiated gastric cancer
US8962655B2 (en) 2007-01-29 2015-02-24 Eisai R&D Management Co., Ltd. Composition for treatment of undifferentiated gastric cancer
US9012458B2 (en) 2010-06-25 2015-04-21 Eisai R&D Management Co., Ltd. Antitumor agent using compounds having kinase inhibitory effect in combination
US9945862B2 (en) 2011-06-03 2018-04-17 Eisai R&D Management Co., Ltd. Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds
US11598776B2 (en) 2011-06-03 2023-03-07 Eisai R&D Management Co., Ltd. Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds
US9334239B2 (en) 2012-12-21 2016-05-10 Eisai R&D Management Co., Ltd. Amorphous form of quinoline derivative, and method for producing same
US10517861B2 (en) 2013-05-14 2019-12-31 Eisai R&D Management Co., Ltd. Biomarkers for predicting and assessing responsiveness of endometrial cancer subjects to lenvatinib compounds
US10259791B2 (en) 2014-08-28 2019-04-16 Eisai R&D Management Co., Ltd. High-purity quinoline derivative and method for manufacturing same
US10407393B2 (en) 2014-08-28 2019-09-10 Eisai R&D Management Co., Ltd. High-purity quinoline derivative and method for manufacturing same
US10822307B2 (en) 2014-08-28 2020-11-03 Eisai R&D Management Co., Ltd. High-purity quinoline derivative and method for manufacturing same
US11186547B2 (en) 2014-08-28 2021-11-30 Eisai R&D Management Co., Ltd. High-purity quinoline derivative and method for manufacturing same
US11090386B2 (en) 2015-02-25 2021-08-17 Eisai R&D Management Co., Ltd. Method for suppressing bitterness of quinoline derivative
US11547705B2 (en) 2015-03-04 2023-01-10 Merck Sharp & Dohme Llc Combination of a PD-1 antagonist and a VEGF-R/FGFR/RET tyrosine kinase inhibitor for treating cancer
US12083112B2 (en) 2015-03-04 2024-09-10 Eisai R&D Management Co., Ltd. Combination of a PD-1 antagonist and a VEGFR/FGFR/RET tyrosine kinase inhibitor for treating cancer
US11369623B2 (en) 2015-06-16 2022-06-28 Prism Pharma Co., Ltd. Anticancer combination of a CBP/catenin inhibitor and an immune checkpoint inhibitor

Also Published As

Publication number Publication date
EP2364699A1 (en) 2011-09-14
EP1797877A4 (en) 2010-12-15
WO2006030947A1 (en) 2006-03-23
WO2006030941A1 (en) 2006-03-23

Similar Documents

Publication Publication Date Title
US8772269B2 (en) Use of sulfonamide-including compounds in combination with angiogenesis inhibitors
EP1797877A1 (en) Joint use of sulfonamide based compound with angiogenesis inhibitor
JP4989476B2 (en) Methods for assaying the effects of angiogenesis inhibitors
EP1859793A1 (en) Novel combinational use of sulfonamide compound
CN101316590B (en) Use of combination of anti-angiogenic substance and c-kit kinase inhibitor
CA2676796C (en) Composition for treatment of undifferentiated gastric cancer
AU2006217690B2 (en) Novel use of sulfonamide compound in combination with angiogenesis inhibitor
TW202228700A (en) Methods of treating and preventing alloantibody driven chronic graft versus host disease
US20080286282A1 (en) Novel Use of Sulfonamide Compound in Combination with Angiogenesis Inhibitor
JP5134247B2 (en) Combination of sulfonamide-containing compounds with angiogenesis inhibitors
EA045102B1 (en) APPLICATION OF 1-[4-BROMO-5-[1-ETHYL-7-(METHYLAMINO)-2-OXO-1,2-DIHYDRO-1,6-NAPHYRIDIN-3-YL]-2-FLUOROPHENYL]-3-PHENYLUREA AND ANALOGUES FOR THE TREATMENT OF CANCER ASSOCIATED WITH GENETIC DISORDERS IN THE PLATELET GROWTH FACTOR ALPHA RECEPTOR
WO2006090921A1 (en) Inhibitory effect of sulfonamide compound on lymphocyte activation

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20070403

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA HR MK YU

RIC1 Information provided on ipc code assigned before grant

Ipc: A61K 45/06 20060101ALI20101104BHEP

Ipc: A61P 35/00 20060101ALI20101104BHEP

Ipc: A61P 9/00 20060101ALI20101104BHEP

Ipc: A61K 39/395 20060101ALI20101104BHEP

Ipc: A61K 31/64 20060101ALI20101104BHEP

Ipc: A61K 31/635 20060101ALI20101104BHEP

Ipc: A61K 31/498 20060101ALI20101104BHEP

Ipc: A61K 31/4709 20060101ALI20101104BHEP

Ipc: A61K 31/47 20060101ALI20101104BHEP

Ipc: A61K 31/4439 20060101ALI20101104BHEP

Ipc: A61K 31/404 20060101ALI20101104BHEP

Ipc: A61K 31/381 20060101ALI20101104BHEP

Ipc: A61K 31/18 20060101AFI20101104BHEP

A4 Supplementary search report drawn up and despatched

Effective date: 20101111

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: EISAI R&D MANAGEMENT CO., LTD.

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20110611